Association of Neurokinin-1 Receptor Signaling Pathways with Cancer


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Abstract

Background:Numerous biochemical reactions leading to altered cell proliferation cause tumorigenesis and cancer treatment resistance. The mechanisms implicated include genetic and epigenetic changes, modified intracellular signaling, and failure of control mechanisms caused by intrinsic and extrinsic factors alone or combined. No unique biochemical events are responsible; entangled molecular reactions conduct the resident cells in a tissue to display uncontrolled growth and abnormal migration. Copious experimental research supports the etiological responsibility of NK-1R (neurokinin-1 receptor) activation, alone or cooperating with other mechanisms, in cancer appearance in different tissues. Consequently, a profound study of this receptor system in the context of malignant processes is essential to design new treatments targeting NK-1R-deviated activity.

Methods:This study reviews and discusses recent literature that analyzes the main signaling pathways influenced by the activation of neurokinin 1 full and truncated receptor variants. Also, the involvement of NK-1R in cancer development is discussed.

Conclusion:NK-1R can signal through numerous pathways and cross-talk with other receptor systems. The participation of override or malfunctioning NK-1R in malignant processes needs a more precise definition in different types of cancers to apply satisfactory and effective treatments. A long way has already been traveled: the current disposal of selective and effective NK-1R antagonists and the capacity to develop new drugs with biased agonistic properties based on the receptor's structural states with functional significance opens immediate research action and clinical application.

About the authors

Francisco Rodriguez

Department of Biochemistry and Molecular Biology, Faculty of Chemical Sciences, University of Salamanca

Author for correspondence.
Email: info@benthamscience.net

Rafael Covenas

BMD (Bases Moleculares del Desarrollo), University of Salamanca

Email: info@benthamscience.net

References

  1. Kroemer, G.; Pouyssegur, J. Tumor cell metabolism: Cancer’s Achilles’ heel. Cancer Cell, 2008, 13(6), 472-482. doi: 10.1016/j.ccr.2008.05.005 PMID: 18538731
  2. Revathidevi, S.; Munirajan, A.K. Akt in cancer: Mediator and more. Semin. Cancer Biol., 2019, 59, 80-91. doi: 10.1016/j.semcancer.2019.06.002 PMID: 31173856
  3. Nirmaladevi, R.; Paital, B.; Jayachandran, P.; Padma, P.R.; Nirmaladevi, R. Epigenetic alterations in cancer. Front. Biosci., 2020, 25(6), 1058-1109. doi: 10.2741/4847 PMID: 32114424
  4. GPCR. Database., 2022. Available from: https://gpcrdb.org/protein/nk1r_human (Accessed on: 22 December 2022).
  5. Venkatakrishnan, A.J.; Flock, T.; Prado, D.E.; Oates, M.E.; Gough, J.; Madan Babu, M. Structured and disordered facets of the GPCR fold. Curr. Opin. Struct. Biol., 2014, 27, 129-137. doi: 10.1016/j.sbi.2014.08.002 PMID: 25198166
  6. Wootten, D.; Christopoulos, A.; Sexton, P.M. Emerging paradigms in GPCR allostery: Implications for drug discovery. Nat. Rev. Drug Discov., 2013, 12(8), 630-644. doi: 10.1038/nrd4052 PMID: 23903222
  7. Jiang, H.; Galtes, D.; Wang, J.; Rockman, H.A. G protein-coupled receptor signaling: Transducers and effectors. Am. J. Physiol. Cell Physiol., 2022, 323(3), C731-C748. doi: 10.1152/ajpcell.00210.2022 PMID: 35816644
  8. Engelman, D.M.; Xiao Zhou, F.; Cocco, M.J.; Russ, W.P.; Brunger, A.T. Interhelical hydrogen bonding drives strong interactions in membrane proteins. Nat. Struct. Biol., 2000, 7(2), 154-160. doi: 10.1038/72430 PMID: 10655619
  9. DeWire, S.M.; Ahn, S.; Lefkowitz, R.J.; Shenoy, S.K. Beta-arrestins and cell signaling. Annu. Rev. Physiol., 2007, 69(1), 483-510. doi: 10.1146/annurev.physiol.69.022405.154749 PMID: 17305471
  10. Rajagopal, S.; Rajagopal, K.; Lefkowitz, R.J. Teaching old receptors new tricks: Biasing seven-transmembrane receptors. Nat. Rev. Drug Discov., 2010, 9(5), 373-386. doi: 10.1038/nrd3024 PMID: 20431569
  11. Weis, W.I.; Kobilka, B.K. The molecular basis of G protein-coupled receptor activation. Annu. Rev. Biochem., 2018, 87(1), 897-919. doi: 10.1146/annurev-biochem-060614-033910 PMID: 29925258
  12. Smith, J.S.; Pack, T.F.; Inoue, A.; Lee, C.; Zheng, K.; Choi, I.; Eiger, D.S.; Warman, A.; Xiong, X.; Ma, Z.; Viswanathan, G.; Levitan, I.M.; Rochelle, L.K.; Staus, D.P.; Snyder, J.C.; Kahsai, A.W.; Caron, M.G.; Rajagopal, S. Noncanonical scaffolding of G αi and β-arrestin by G protein–coupled receptors. Science., 2021, 371(6534), eaay1833. doi: 10.1126/science.aay1833 PMID: 33479120
  13. DeVree, B.T.; Mahoney, J.P.; Vélez-Ruiz, G.A.; Rasmussen, S.G.F.; Kuszak, A.J.; Edwald, E.; Fung, J.J.; Manglik, A.; Masureel, M.; Du, Y.; Matt, R.A.; Pardon, E.; Steyaert, J.; Kobilka, B.K.; Sunahara, R.K. Allosteric coupling from G protein to the agonist-binding pocket in GPCRs. Nature, 2016, 535(7610), 182-186. doi: 10.1038/nature18324 PMID: 27362234
  14. Liu, Y.; An, S.; Ward, R.; Yang, Y.; Guo, X.X.; Li, W.; Xu, T.R. G protein-coupled receptors as promising cancer targets. Cancer Lett., 2016, 376(2), 226-239. doi: 10.1016/j.canlet.2016.03.031 PMID: 27000991
  15. Chaudhary, P.K.; Kim, S. An insight into GPCR and G-proteins as cancer drivers. Cells, 2021, 10(12), 3288. doi: 10.3390/cells10123288 PMID: 34943797
  16. Luo, J.; Yu, F.X. GPCR-hippo signaling in cancer. Cells, 2019, 8(5), 426. doi: 10.3390/cells8050426 PMID: 31072060
  17. Kage, R.; Leeman, S.E.; Boyd, N.D. Biochemical characterization of two different forms of the substance P receptor in rat submaxillary gland. J. Neurochem., 1993, 60(1), 347-351. doi: 10.1111/j.1471-4159.1993.tb05857.x PMID: 8380195
  18. Holst, B.; Nygaard, R.; Valentin-Hansen, L.; Bach, A.; Engelstoft, M.S.; Petersen, P.S.; Frimurer, T.M.; Schwartz, T.W. A conserved aromatic lock for the tryptophan rotameric switch in TM-VI of seven-transmembrane receptors. J. Biol. Chem., 2010, 285(6), 3973-3985. doi: 10.1074/jbc.M109.064725 PMID: 19920139
  19. UniProt Database. 2022. Available from: https://www.uniprot.org/uniprot/P25103 (Accessed on: 22 December 2022).
  20. Gayen, A.; Goswami, S.K.; Mukhopadhyay, C. NMR evidence of GM1-induced conformational change of Substance P using isotropic bicelles. Biochim. Biophys. Acta Biomembr., 2011, 1808(1), 127-139. doi: 10.1016/j.bbamem.2010.09.023 PMID: 20937248
  21. V Euler, U.S.; Gaddum, J.H. An unidentified depressor substance in certain tissue extracts. J. Physiol., 1931, 72(1), 74-87. doi: 10.1113/jphysiol.1931.sp002763 PMID: 16994201
  22. Severini, C.; Improta, G.; Falconieri-Erspamer, G.; Salvadori, S.; Erspamer, V. The tachykinin peptide family. Pharmacol. Rev., 2002, 54(2), 285-322. doi: 10.1124/pr.54.2.285 PMID: 12037144
  23. Almeida, T.A.; Rojo, J.; Nieto, P.M.; Pinto, F.M.; Hernandez, M.; Martín, J.D.; Candenas, M.L. Tachykinins and tachykinin receptors: Structure and activity relationships. Curr. Med. Chem., 2004, 11(15), 2045-2081. doi: 10.2174/0929867043364748 PMID: 15279567
  24. Zhang, Y.; Lu, L.; Furlonger, C.; Wu, G.E.; Paige, C.J. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nat. Immunol., 2000, 1(5), 392-397. doi: 10.1038/80826 PMID: 11062498
  25. Borbély, É.; Helyes, Z. Role of hemokinin-1 in health and disease. Neuropeptides, 2017, 64, 9-17. doi: 10.1016/j.npep.2016.12.003 PMID: 27993375
  26. Mussap, C.J.; Geraghty, D.P.; Burcher, E. Tachykinin receptors: A radioligand binding perspective. J. Neurochem., 1993, 60(6), 1987-2009. doi: 10.1111/j.1471-4159.1993.tb03484.x PMID: 8388031
  27. Pennefather, J.N.; Lecci, A.; Candenas, M.L.; Patak, E.; Pinto, F.M.; Maggi, C.A. Tachykinins and tachykinin receptors: A growing family. Life Sci., 2004, 74(12), 1445-1463. doi: 10.1016/j.lfs.2003.09.039 PMID: 14729395
  28. Preininger, A.M.; Meiler, J.; Hamm, H.E. Conformational flexibility and structural dynamics in GPCR-mediated G protein activation: A perspective. J. Mol. Biol., 2013, 425(13), 2288-2298. doi: 10.1016/j.jmb.2013.04.011 PMID: 23602809
  29. Pándy-Szekeres, G.; Esguerra, M.; Hauser, A.S.; Caroli, J.; Munk, C.; Pilger, S.; Keserű, G.M.; Kooistra, A.J.; Gloriam, D.E. The G protein database, GproteinDb. Nucleic Acids Res., 2022, 50(D1), D518-D525. doi: 10.1093/nar/gkab852 PMID: 34570219
  30. Deng, X.T.; Tang, S.M.; Wu, P.Y.; Li, Q.P.; Ge, X.X.; Xu, B.M.; Wang, H.S.; Miao, L. SP/NK-1R promotes gallbladder cancer cell proliferation and migration. J. Cell. Mol. Med., 2019, 23(12), 7961-7973. doi: 10.1111/jcmm.14230 PMID: 30903649
  31. Muñoz, M.; Rosso, M.; Coveñas, R. Neurokinin-1 receptor antagonists against hepatoblastoma. Cancers., 2019, 11(9), 1258. doi: 10.3390/cancers11091258 PMID: 31466222
  32. Muñoz, M.; Coveñas, R. Coveñas, R. The neurokinin-1 receptor antagonist aprepitant: An intelligent bullet against cancer? Cancers., 2020, 12(9), 2682. doi: 10.3390/cancers12092682 PMID: 32962202
  33. Isorna, I.; Esteban, F.; Solanellas, J.; Coveñas, R.; Muñoz, M. The substance P and neurokinin-1 receptor system in human thyroid cancer: An immunohistochemical study. Eur. J. Histochem., 2020, 64(2), 3117. doi: 10.4081/ejh.2020.3117 PMID: 32363847
  34. Esteban, F.; Ramos-García, P.; Muñoz, M.; González-Moles, M.Á. Substance P and neurokinin 1 receptor in chronic inflammation and cancer of the head and neck: A Review of the literature. Int. J. Environ. Res. Public Health, 2021, 19(1), 375. doi: 10.3390/ijerph19010375 PMID: 35010633
  35. Coveñas, R.; Muñoz, M. Involvement of the substance P/neurokinin-1 receptor system in cancer. Cancers., 2022, 14(14), 3539. doi: 10.3390/cancers14143539 PMID: 35884599
  36. García-Aranda, M.; Téllez, T.; McKenna, L.; Redondo, M. Neurokinin-1 receptor (NK-1R) antagonists as a new strategy to overcome cancer resistance. Cancers., 2022, 14(9), 2255. doi: 10.3390/cancers14092255 PMID: 35565383
  37. Ji, T.; Ma, K.; Wu, H.; Cao, T.; Substance, P. (SP)/neurokinin-1 receptor axis promotes perineural invasion of pancreatic cancer and is affected by lncRNA LOC389641. J. Immunol. Res., 2022, 2022, 1-17. doi: 10.1155/2022/5582811 PMID: 35600049
  38. Muñoz, M.; Rosso, M.; Coveñas, R. Triple negative breast cancer: How neurokinin-1 receptor antagonists could be used as a new therapeutic approach. Mini Rev. Med. Chem., 2020, 20(5), 408-417. doi: 10.2174/1389557519666191112152642 PMID: 31721701
  39. Ebrahimi, S.; Mirzavi, F.; Aghaee-Bakhtiari, S.H.; Hashemy, S.I. SP/NK1R system regulates carcinogenesis in prostate cancer: Shedding light on the antitumoral function of aprepitant. Biochim. Biophys. Acta Mol. Cell Res., 2022, 1869(5), 119221. doi: 10.1016/j.bbamcr.2022.119221 PMID: 35134443
  40. Rodriguez, E.; Pei, G.; Zhao, Z.; Kim, S.; German, A.; Robinson, P. Substance P antagonism as a novel therapeutic option to enhance efficacy of cisplatin in triple negative breast cancer and protect PC12 cells against cisplatin-induced oxidative stress and apoptosis. Cancers., 2021, 13(15), 3871. doi: 10.3390/cancers13153871 PMID: 34359773
  41. Zhang, X.W.; Li, L.; Hu, W.Q.; Hu, M.N.; Tao, Y.; Hu, H.; Miao, X.K.; Yang, W.L.; Zhu, Q.; Mou, L.Y. Neurokinin-1 receptor promotes non-small cell lung cancer progression through transactivation of EGFR. Cell Death Dis., 2022, 13(1), 41. doi: 10.1038/s41419-021-04485-y PMID: 35013118
  42. DeFea, K.A.; Vaughn, Z.D.; O’Bryan, E.M.; Nishijima, D.; Déry, O.; Bunnett, N.W. The proliferative and antiapoptotic effects of substance P are facilitated by formation of a β-arrestin-dependent scaffolding complex. Proc. Natl. Acad. Sci., 2000, 97(20), 11086-11091. doi: 10.1073/pnas.190276697 PMID: 10995467
  43. Pal, K.; Mathur, M.; Kumar, P.; DeFea, K. Divergent β-arrestin-dependent signaling events are dependent upon sequences within G-protein-coupled receptor C termini. J. Biol. Chem., 2013, 288(5), 3265-3274. doi: 10.1074/jbc.M112.400234 PMID: 23235155
  44. Guo, S.; Zhao, T.; Yun, Y.; Xie, X. Recent progress in assays for GPCR drug discovery. Am. J. Physiol. Cell Physiol., 2022, 323(2), C583-C594. doi: 10.1152/ajpcell.00464.2021 PMID: 35816640
  45. Stamm, S.; Gruber, S.B.; Rabchevsky, A.G.; Emeson, R.B. The activity of the serotonin receptor 2C is regulated by alternative splicing. Hum. Genet., 2017, 136(9), 1079-1091. doi: 10.1007/s00439-017-1826-3 PMID: 28664341
  46. Valentin-Hansen, L.; Frimurer, T.M.; Mokrosinski, J.; Holliday, N.D.; Schwartz, T.W. Biased Gs versus Gq proteins and β-arrestin signaling in the NK1 receptor determined by interactions in the water hydrogen bond network. J. Biol. Chem., 2015, 290(40), 24495-24508. doi: 10.1074/jbc.M115.641944 PMID: 26269596
  47. Smith, J.S.; Lefkowitz, R.J.; Rajagopal, S. Biased signalling: From simple switches to allosteric microprocessors. Nat. Rev. Drug Discov., 2018, 17(4), 243-260. doi: 10.1038/nrd.2017.229 PMID: 29302067
  48. Wootten, D.; Christopoulos, A.; Marti-Solano, M.; Babu, M.M.; Sexton, P.M. Mechanisms of signalling and biased agonism in G protein-coupled receptors. Nat. Rev. Mol. Cell Biol., 2018, 19(10), 638-653. doi: 10.1038/s41580-018-0049-3 PMID: 30104700
  49. Alvarez-Curto, E.; Inoue, A.; Jenkins, L.; Raihan, S.Z.; Prihandoko, R.; Tobin, A.B.; Milligan, G. Targeted elimination of G proteins and arrestins defines their specific contributions to both intensity and duration of G protein-coupled receptor signaling. J. Biol. Chem., 2016, 291(53), 27147-27159. doi: 10.1074/jbc.M116.754887 PMID: 27852822
  50. Liggett, S.B. Phosphorylation barcoding as a mechanism of directing GPCR signaling. Sci. Signal., 2011, 4(185), pe36. doi: 10.1126/scisignal.2002331 PMID: 21868354
  51. Steinhoff, M.S.; von Mentzer, B.; Geppetti, P.; Pothoulakis, C.; Bunnett, N.W. Tachykinins and their receptors: Contributions to physiological control and the mechanisms of disease. Physiol. Rev., 2014, 94(1), 265-301. doi: 10.1152/physrev.00031.2013 PMID: 24382888
  52. Valentin-Hansen, L.; Park, M.; Huber, T.; Grunbeck, A.; Naganathan, S.; Schwartz, T.W.; Sakmar, T.P. Mapping substance P binding sites on the neurokinin-1 receptor using genetic incorporation of a photoreactive amino acid. J. Biol. Chem., 2014, 289(26), 18045-18054. doi: 10.1074/jbc.M113.527085 PMID: 24831006
  53. Garcia-Recio, S.; Gascón, P. Biological and pharmacological aspects of the NK1-receptor. BioMed Res. Int., 2015, 2015, 1-14. doi: 10.1155/2015/495704 PMID: 26421291
  54. Spitsin, S.; Pappa, V.; Douglas, S.D. Truncation of neurokinin-1 receptor—Negative regulation of substance P signaling. J. Leukoc. Biol., 2018, 103(6), 1043-1051. doi: 10.1002/JLB.3MIR0817-348R PMID: 29345372
  55. Javid, H.; Asadi, J.; Zahedi Avval, F.; Afshari, A.R.; Hashemy, S.I. The role of substance P/neurokinin 1 receptor in the pathogenesis of esophageal squamous cell carcinoma through constitutively active PI3K/Akt/NF-κB signal transduction pathways. Mol. Biol. Rep., 2020, 47(3), 2253-2263. doi: 10.1007/s11033-020-05330-9 PMID: 32072401
  56. Ebrahimi, S.; Javid, H.; Alaei, A.; Hashemy, S.I. New insight into the role of substance P/neurokinin-1 receptor system in breast cancer progression and its crosstalk with MICRORNAS. Clin. Genet., 2020, 98(4), 322-330. doi: 10.1111/cge.13750 PMID: 32266968
  57. Ballesteros, J.A.; Weinstein, H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. J. Neurosci. Methods, 1995, 25, 366-428. doi: 10.1016/S1043-9471(05)80049-7
  58. Harris, J.A.; Faust, B.; Gondin, A.B.; Dämgen, M.A.; Suomivuori, C.M.; Veldhuis, N.A.; Cheng, Y.; Dror, R.O.; Thal, D.M.; Manglik, A. Selective G protein signaling driven by substance P–neurokinin receptor dynamics. Nat. Chem. Biol., 2022, 18(1), 109-115. doi: 10.1038/s41589-021-00890-8 PMID: 34711980
  59. Rodriguez, F.D; Coveñas, R. The neurokinin-1 receptor: Structure dynamics and signaling. Receptors., 2022, 1(1), 54-71. doi: 10.3390/receptors1010004
  60. PDB. Protein Data Bank. 2022. Available from: https://pdb101.rcsb.org
  61. Sehnal, D.; Bittrich, S.; Deshpande, M.; Svobodová, R.; Berka, K.; Bazgier, V.; Velankar, S.; Burley, S.K.; Koča, J.; Rose, A.S. Mol* Viewer: Modern web app for 3D visualization and analysis of large biomolecular structures. Nucleic Acids Res., 2021, 49(W1), W431-W437. doi: 10.1093/nar/gkab314 PMID: 33956157
  62. Jean-Charles, P.Y.; Kaur, S.; Shenoy, S.K. Protein-coupled receptor signaling through β-Arrestin-dependent mechanisms. J. Cardiovasc. Pharmacol., 2017, 70(3), 142-158. doi: 10.1097/FJC.0000000000000482 PMID: 28328745
  63. Shukla, A.K.; Dwivedi-Agnihotri, H. Structure and function of β-arrestins, their emerging role in breast cancer, and potential opportunities for therapeutic manipulation. Adv. Cancer Res., 2020, 145, 139-156. doi: 10.1016/bs.acr.2020.01.001 PMID: 32089163
  64. Perry-Hauser, N.A.; Hopkins, J.B.; Zhuo, Y.; Zheng, C.; Perez, I.; Schultz, K.M.; Vishnivetskiy, S.A.; Kaya, A.I.; Sharma, P.; Dalby, K.N.; Chung, K.Y.; Klug, C.S.; Gurevich, V.V.; Iverson, T.M. The two non-visual arrestins engage ERK2 differently. J. Mol. Biol., 2022, 434(7), 167465. doi: 10.1016/j.jmb.2022.167465 PMID: 35077767
  65. Xiao, K.; McClatchy, D.B.; Shukla, A.K.; Zhao, Y.; Chen, M.; Shenoy, S.K.; Yates, J.R., III; Lefkowitz, R.J. Functional specialization of β-arrestin interactions revealed by proteomic analysis. Proc. Natl. Acad. Sci., 2007, 104(29), 12011-12016. doi: 10.1073/pnas.0704849104 PMID: 17620599
  66. Peterson, Y.K.; Luttrell, L.M. The diverse roles of arrestin scaffolds in G protein-coupled receptor signaling. Pharmacol. Rev., 2017, 69(3), 256-297. doi: 10.1124/pr.116.013367 PMID: 28626043
  67. Ghosh, E.; Dwivedi, H.; Baidya, M.; Srivastava, A.; Kumari, P.; Stepniewski, T.; Kim, H.R.; Lee, M.H.; van Gastel, J.; Chaturvedi, M.; Roy, D.; Pandey, S.; Maharana, J.; Guixà-González, R.; Luttrell, L.M.; Chung, K.Y.; Dutta, S.; Selent, J.; Shukla, A.K. Conformational sensors and domain swapping reveal structural and functional differences between β-Arrestin isoforms. Cell Rep., 2019, 28(13), 3287-3299.e6. doi: 10.1016/j.celrep.2019.08.053 PMID: 31553900
  68. Wess, J. The two β-arrestins regulate distinct metabolic processes: Studies with novel mutant mouse models. Int. J. Mol. Sci., 2022, 23(1), 495. doi: 10.3390/ijms23010495 PMID: 35008921
  69. Han, M.; Gurevich, V.V.; Vishnivetskiy, S.A.; Sigler, P.B.; Schubert, C. Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane Translocation. Structure, 2001, 9(9), 869-880. doi: 10.1016/S0969-2126(01)00644-X PMID: 11566136
  70. Milano, S.K.; Pace, H.C.; Kim, Y.M.; Brenner, C.; Benovic, J.L. Scaffolding functions of arrestin-2 revealed by crystal structure and mutagenesis. Biochemistry, 2002, 41(10), 3321-3328. doi: 10.1021/bi015905j PMID: 11876640
  71. Shenoy, S.K.; Lefkowitz, R.J. Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. J. Biol. Chem., 2003, 278(16), 14498-14506. doi: 10.1074/jbc.M209626200 PMID: 12574160
  72. Shenoy, S.K.; Lefkowitz, R.J. Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes. J. Biol. Chem., 2005, 280(15), 15315-15324. doi: 10.1074/jbc.M412418200 PMID: 15699045
  73. Kim, K.; Han, Y.; Duan, L.; Chung, K.Y. Scaffolding of mitogen-activated protein kinase signaling by β-arrestins. Int. J. Mol. Sci., 2022, 23(2), 1000. doi: 10.3390/ijms23021000 PMID: 35055186
  74. Cahill, T.J., III; Thomsen, A.R.B.; Tarrasch, J.T.; Plouffe, B.; Nguyen, A.H.; Yang, F.; Huang, L.Y.; Kahsai, A.W.; Bassoni, D.L.; Gavino, B.J.; Lamerdin, J.E.; Triest, S.; Shukla, A.K.; Berger, B.; Little, J., IV; Antar, A.; Blanc, A.; Qu, C.X.; Chen, X.; Kawakami, K.; Inoue, A.; Aoki, J.; Steyaert, J.; Sun, J.P.; Bouvier, M.; Skiniotis, G.; Lefkowitz, R.J. Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis. Proc. Natl. Acad. Sci., 2017, 114(10), 2562-2567. doi: 10.1073/pnas.1701529114 PMID: 28223524
  75. Seckler, J.M.; Robinson, E.N.; Lewis, S.J.; Grossfield, A. Surveying nonvisual arrestins reveals allosteric interactions between functional sites. Proteins, 2023, 91(1), 99-107. doi: 10.1002/prot.26413 PMID: 35988049
  76. Yang, Z.; Yang, F.; Zhang, D.; Liu, Z.; Lin, A.; Liu, C.; Xiao, P.; Yu, X.; Sun, J.P. Phosphorylation of G protein-coupled receptors: From the barcode hypothesis to the flute model. Mol. Pharmacol., 2017, 92(3), 201-210. doi: 10.1124/mol.116.107839 PMID: 28246190
  77. Jean-Charles, P.Y.; Rajiv, V.; Sarker, S.; Han, S.; Bai, Y.; Masoudi, A.; Shenoy, S.K. A single phenylalanine residue in β-arrestin2 critically regulates its binding to G protein–coupled receptors. J. Biol. Chem., 2022, 298(5), 101837. doi: 10.1016/j.jbc.2022.101837 PMID: 35307348
  78. Kawakami, K.; Yanagawa, M.; Hiratsuka, S.; Yoshida, M.; Ono, Y.; Hiroshima, M.; Ueda, M.; Aoki, J.; Sako, Y.; Inoue, A. Heterotrimeric Gq proteins act as a switch for GRK5/6 selectivity underlying β-arrestin transducer bias. Nat. Commun., 2022, 13(1), 487. doi: 10.1038/s41467-022-28056-7 PMID: 35078997
  79. Sarma, P.; Saha, S.; Shukla, A.K. Making the switch: The role of Gq in driving GRK selectivity at GPCRs. Sci. Signal., 2022, 15(726), eabo4949. doi: 10.1126/scisignal.abo4949 PMID: 35316098
  80. Grundmann, M.; Merten, N.; Malfacini, D.; Inoue, A.; Preis, P.; Simon, K.; Rüttiger, N.; Ziegler, N.; Benkel, T.; Schmitt, N.K.; Ishida, S.; Müller, I.; Reher, R.; Kawakami, K.; Inoue, A.; Rick, U.; Kühl, T.; Imhof, D.; Aoki, J.; König, G.M.; Hoffmann, C.; Gomeza, J.; Wess, J.; Kostenis, E. Lack of beta-arrestin signaling in the absence of active G proteins. Nat. Commun., 2018, 9(1), 341-343. doi: 10.1038/s41467-017-02661-3 PMID: 29362459
  81. Zhu, L.; Almaça, J.; Dadi, P.K.; Hong, H.; Sakamoto, W.; Rossi, M.; Lee, R.J.; Vierra, N.C.; Lu, H.; Cui, Y.; McMillin, S.M.; Perry, N.A.; Gurevich, V.V.; Lee, A.; Kuo, B.; Leapman, R.D.; Matschinsky, F.M.; Doliba, N.M.; Urs, N.M.; Caron, M.G.; Jacobson, D.A.; Caicedo, A.; Wess, J. β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions. Nat. Commun., 2017, 8(1), 14295-, 8, 14295. doi: 10.1038/ncomms14295 PMID: 28145434
  82. Zhang, Y.X.; Li, X.F.; Yuan, G.Q.; Hu, H.; Song, X.Y.; Li, J.Y.; Miao, X.K.; Zhou, T.X.; Yang, W.L.; Zhang, X.W.; Mou, L.Y.; Wang, R. β-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G2/M phase transition. J. Biol. Chem., 2017, 292(21), 8933-8947. doi: 10.1074/jbc.M116.770420 PMID: 28341744
  83. Jafri, F.; El-Shewy, H.M.; Lee, M.H.; Kelly, M.; Luttrell, D.K.; Luttrell, L.M. Constitutive ERK1/2 activation by a chimeric neurokinin 1 receptor-beta-arrestin1 fusion protein. Probing the composition and function of the G protein-coupled receptor "signalsome". J. Biol. Chem., 2006, 281(28), 19346-19357. doi: 10.1074/jbc.M512643200 PMID: 16670094
  84. Schmidlin, F.; Roosterman, D.; Bunnett, N.W. The third intracellular loop and carboxyl tail of neurokinin 1 and 3 receptors determine interactions with β-arrestins. Am. J. Physiol. Cell Physiol., 2003, 285(4), C945-C958. doi: 10.1152/ajpcell.00541.2002 PMID: 12958028
  85. Bagnato, A.; Rosanò, L. Rosanò, L. New routes in GPCR/β-arrestin-driven signaling in cancer progression and metastasis. Front. Pharmacol., 2019, 10, 114. doi: 10.3389/fphar.2019.00114 PMID: 30837880
  86. Foord, S.M.; Bonner, T.I.; Neubig, R.R.; Rosser, E.M.; Pin, J.P.; Davenport, A.P.; Spedding, M.; Harmar, A.J. International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol. Rev., 2005, 57(2), 279-288. doi: 10.1124/pr.57.2.5 PMID: 15914470
  87. Campbell, A.P.; Smrcka, A.V. Targeting G protein-coupled receptor signalling by blocking G proteins. Nat. Rev. Drug Discov., 2018, 17(11), 789-803. doi: 10.1038/nrd.2018.135 PMID: 30262890
  88. Khan, S.M.; Sleno, R.; Gora, S.; Zylbergold, P.; Laverdure, J.P.; Labbé, J.C.; Miller, G.J.; Hébert, T.E. The expanding roles of Gβγ subunits in G protein-coupled receptor signaling and drug action. Pharmacol. Rev., 2013, 65(2), 545-577. doi: 10.1124/pr.111.005603 PMID: 23406670
  89. Tennakoon, M.; Senarath, K.; Kankanamge, D.; Ratnayake, K.; Wijayaratna, D.; Olupothage, K.; Ubeysinghe, S.; Martins-Cannavino, K.; Hébert, T.E.; Karunarathne, A. Subtype-dependent regulation of Gβγ signalling. Cell. Signal., 2021, 82, 109947. doi: 10.1016/j.cellsig.2021.109947 PMID: 33582184
  90. Harris, G.C.; Aston-Jones, G. Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome. Nature, 1994, 371(6493), 155-157. doi: 10.1038/371155a0 PMID: 7915401
  91. Thom, C.; Ehrenmann, J.; Vacca, S.; Waltenspühl, Y.; Schöppe, J.; Medalia, O.; Plückthun, A. Structures of neurokinin 1 receptor in complex with G q and G s proteins reveal substance P binding mode and unique activation features. Sci. Adv., 2021, 7(50), eabk2872. doi: 10.1126/sciadv.abk2872 PMID: 34878828
  92. Inoue, A.; Raimondi, F.; Kadji, F.M.N.; Singh, G.; Kishi, T.; Uwamizu, A.; Ono, Y.; Shinjo, Y.; Ishida, S.; Arang, N.; Kawakami, K.; Gutkind, J.S.; Aoki, J.; Russell, R.B. Illuminating G-protein-coupling selectivity of GPCRs. Cell, 2019, 177(7), 1933-1947.e25. doi: 10.1016/j.cell.2019.04.044 PMID: 31160049
  93. Senarath, K.; Kankanamge, D.; Samaradivakara, S.; Ratnayake, K.; Tennakoon, M.; Karunarathne, A. regulation of G protein βγ signaling. Int. Rev. Cell Mol. Biol., 2018, 339, 133-191. doi: 10.1016/bs.ircmb.2018.02.008 PMID: 29776603
  94. Khan, S.M.; Sung, J.Y.; Hébert, T.E. Gβγ subunits-different spaces, different faces. Pharmacol. Res., 2016, 111, 434-441. doi: 10.1016/j.phrs.2016.06.026 PMID: 27378564
  95. Khater, M.; Bryant, C.N.; Wu, G. Gβγ translocation to the Golgi apparatus activates ARF1 to spatiotemporally regulate G protein–coupled receptor signaling to MAPK. J. Biol. Chem., 2021, 296, 100805. doi: 10.1016/j.jbc.2021.100805 PMID: 34022220
  96. Smrcka, A.V. G protein βγ subunits: Central mediators of G protein-coupled receptor signaling. Cell. Mol. Life Sci., 2008, 65(14), 2191-2214. doi: 10.1007/s00018-008-8006-5 PMID: 18488142
  97. Klayman, L.M.; Wedegaertner, P.B. Wedegaertner, P. B. Inducible inhibition of Gβγ reveals localization-dependent functions at the plasma membrane and Golgi. J. Biol. Chem., 2017, 292(5), 1773-1784. doi: 10.1074/jbc.M116.750430 PMID: 27994056
  98. Rajanala, K.; Klayman, L.M.; Wedegaertner, P.B. Gβγ regulates mitotic Golgi fragmentation and G2/M cell cycle progression. Mol. Biol. Cell, 2021, 32(20), br2. doi: 10.1091/mbc.E21-04-0175 PMID: 34260268
  99. Madukwe, J.C.; Garland-Kuntz, E.E.; Lyon, A.M.; Smrcka, A.V. G protein βγ subunits directly interact with and activate phospholipase CΕ. J. Biol. Chem., 2018, 293(17), 6387-6397. doi: 10.1074/jbc.RA118.002354 PMID: 29535186
  100. Gont, A.; Daneshmand, M.; Woulfe, J.; Lavictoire, S.J.; Lorimer, I.A.J. PREX1 integrates G protein-coupled receptor and phosphoinositide 3-kinase signaling to promote glioblastoma invasion. Oncotarget, 2017, 8(5), 8559-8573. doi: 10.18632/oncotarget.14348 PMID: 28051998
  101. Pfeil, E.M.; Brands, J.; Merten, N.; Vögtle, T.; Vescovo, M.; Rick, U.; Albrecht, I.M.; Heycke, N.; Kawakami, K.; Ono, Y.; Ngako Kadji, F.M.; Hiratsuka, S.; Aoki, J.; Häberlein, F.; Matthey, M.; Garg, J.; Hennen, S.; Jobin, M.L.; Seier, K.; Calebiro, D.; Pfeifer, A.; Heinemann, A.; Wenzel, D.; König, G.M.; Nieswandt, B.; Fleischmann, B.K.; Inoue, A.; Simon, K.; Kostenis, E. Heterotrimeric G protein subunit Gαq is a master switch for Gβγ-mediated calcium mobilization by Gi-coupled GPCRs. Mol. Cell, 2020, 80(6), 940-954.e6. doi: 10.1016/j.molcel.2020.10.027 PMID: 33202251
  102. Birnbaumer, L. Expansion of signal transduction by G proteins. Biochim. Biophys. Acta Biomembr., 2007, 1768(4), 772-793. doi: 10.1016/j.bbamem.2006.12.002 PMID: 17258171
  103. Davis, T.L.; Bonacci, T.M.; Sprang, S.R.; Smrcka, A.V. Structural and molecular characterization of a preferred protein interaction surface on G protein beta gamma subunits. Biochemistry, 2005, 44(31), 10593-10604. doi: 10.1021/bi050655i PMID: 16060668
  104. Downward, J. Targeting RAS signalling pathways in cancer therapy. Nat. Rev. Cancer, 2003, 3(1), 11-22. doi: 10.1038/nrc969 PMID: 12509763
  105. Zhang, W.; Liu, H.T. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res., 2002, 12(1), 9-18. doi: 10.1038/sj.cr.7290105 PMID: 11942415
  106. Barbosa, R.; Acevedo, L.A.; Marmorstein, R. The MEK/ERK network as a therapeutic target in human cancer. Mol. Cancer Res., 2021, 19(3), 361-374. doi: 10.1158/1541-7786.MCR-20-0687 PMID: 33139506
  107. Chen, Q.; Kong, L.; Xu, Z.; Cao, N.; Tang, X.; Gao, R.; Zhang, J.; Deng, S.; Tan, C.; Zhang, M.; Wang, Y.; Zhang, L.; Ma, K.; Li, L.; Si, J. The role of TMEM16A/ERK/NK-1 signaling in dorsal root ganglia neurons in the development of neuropathic pain induced by spared nerve injury (SNI). Mol. Neurobiol., 2021, 58(11), 5772-5789. doi: 10.1007/s12035-021-02520-9 PMID: 34406600
  108. Mazein, A.; Rougny, A.; Karr, J.R.; Saez-Rodriguez, J.; Ostaszewski, M.; Schneider, R. Reusability and composability in process description maps: RAS–RAF–MEK–ERK signalling. Brief. Bioinform., 2021, 22(5), bbab103. doi: 10.1093/bib/bbab103 PMID: 33834185
  109. Roberts, P.J.; Der, C.J. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene, 2007, 26(22), 3291-3310. doi: 10.1038/sj.onc.1210422 PMID: 17496923
  110. Avery, T.Y.; Köhler, N.; Zeiser, R.; Brummer, T.; Ruess, D.A. Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation. Front. Oncol., 2022, 12, 931774. doi: 10.3389/fonc.2022.931774 PMID: 35965494
  111. Wan, W.; Xiao, W.; Pan, W.; Chen, L.; Liu, Z.; Xu, J. Isoprenylcysteine carboxyl methyltransferase is critical for glioblastoma growth and survival by activating Ras/Raf/Mek/Erk. Cancer Chemother. Pharmacol., 2022, 89(3), 401-411. doi: 10.1007/s00280-022-04401-x PMID: 35171349
  112. Gao, Z.; Chen, J.F.; Li, X.G.; Shi, Y.H.; Tang, Z.; Liu, W.R.; Zhang, X.; Huang, A.; Luo, X.M.; Gao, Q.; Shi, G.M.; Ke, A.W.; Zhou, J.; Fan, J.; Fu, X.T.; Ding, Z.B. KRAS acting through ERK signaling stabilizes PD-L1 via inhibiting autophagy pathway in intrahepatic cholangiocarcinoma. Cancer Cell Int., 2022, 22(1), 128. doi: 10.1186/s12935-022-02550-w PMID: 35305624
  113. Yadav, D.K. Editorial: Kinase inhibitors in cancer therapy. Front. Cell Dev. Biol., 2022, 10, 1020297. doi: 10.3389/fcell.2022.1020297 PMID: 36393866
  114. Vendramini, E.; Bomben, R.; Pozzo, F.; Bittolo, T.; Tissino, E.; Gattei, V.; Zucchetto, A. KRAS and RAS-MAPK pathway deregulation in mature B cell lymphoproliferative disorders. Cancers., 2022, 14(3), 666. doi: 10.3390/cancers14030666 PMID: 35158933
  115. Atif, M.; Mustaan, M.A.; Falak, S.; Ghaffar, A.; Munir, B. Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line. Saudi J. Biol. Sci., 2022, 29(8), 103332. doi: 10.1016/j.sjbs.2022.103332 PMID: 35813116
  116. Asati, V.; Mahapatra, D.K.; Bharti, S.K. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. Eur. J. Med. Chem., 2016, 109, 314-341. doi: 10.1016/j.ejmech.2016.01.012 PMID: 26807863
  117. Yamaguchi, K.; Richardson, M.D.; Bigner, D.D.; Kwatra, M.M. Signal transduction through substance P receptor in human glioblastoma cells: roles for Src and PKCδ. Cancer Chemother. Pharmacol., 2005, 56(6), 585-593. doi: 10.1007/s00280-005-1030-3 PMID: 16012865
  118. Degirmenci, U.; Wang, M.; Hu, J. Targeting aberrant RAS/RAF/MEK/ERK signaling for cancer therapy. Cells, 2020, 9(1), 198. doi: 10.3390/cells9010198 PMID: 31941155
  119. Williams, R.; Zou, X.; Hoyle, G.W. Tachykinin-1 receptor stimulates proinflammatory gene expression in lung epithelial cells through activation of NF-κB via a G q -dependent pathway. Am. J. Physiol. Lung Cell. Mol. Physiol., 2007, 292(2), L430-L437. doi: 10.1152/ajplung.00475.2005 PMID: 17041011
  120. Asl, E.R.; Amini, M.; Najafi, S.; Mansoori, B.; Mokhtarzadeh, A.; Mohammadi, A.; Lotfinejad, P.; Bagheri, M.; Shirjang, S.; Lotfi, Z.; Rasmi, Y.; Baradaran, B. Interplay between MAPK/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression. Life Sci., 2021, 278, 119499. doi: 10.1016/j.lfs.2021.119499 PMID: 33865878
  121. Muñoz, M.; González-Ortega, A.; Salinas-Martín, M.V.; Carranza, A.; Garcia-Recio, S.; Almendro, V.; Coveñas, R. The neurokinin-1 receptor antagonist aprepitant is a promising candidate for the treatment of breast cancer. Int. J. Oncol., 2014, 45(4), 1658-1672. doi: 10.3892/ijo.2014.2565 PMID: 25175857
  122. Yue, J.; López, J.M. Understanding MAPK signaling pathways in apoptosis. Int. J. Mol. Sci., 2020, 21(7), 2346. doi: 10.3390/ijms21072346 PMID: 32231094
  123. Tangchirakhaphan, S.; Innajak, S.; Nilwarangkoon, S.; Tanjapatkul, N.; Mahabusrakum, W.; Watanapokasin, R. Mechanism of apoptosis induction associated with ERK1/2 upregulation via goniothalamin in melanoma cells. Exp. Ther. Med., 2018, 15(3), 3052-3058. doi: 10.3892/etm.2018.5762 PMID: 29456710
  124. Golestaneh, M.; Firoozrai, M.; Javid, H.; Hashemy, S.I. The substance P/ neurokinin-1 receptor signaling pathway mediates metastasis in human colorectal SW480 cancer cells. Mol. Biol. Rep., 2022, 49(6), 4893-4900. doi: 10.1007/s11033-022-07348-7 PMID: 35429316
  125. Ma, J.; Yuan, S.; Cheng, J.; Kang, S.; Zhao, W.; Zhang, J. Substance P promotes the progression of endometrial adenocarcinoma. Int. J. Gynecol. Cancer, 2016, 26(5), 845-850. doi: 10.1097/IGC.0000000000000683 PMID: 27051050
  126. Genersch, E.; Hayeß, K.; Neuenfeld, Y.; Haller, H. Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and-independent pathways. J. Cell Sci., 2000, 113(23), 4319-4330. doi: 10.1242/jcs.113.23.4319 PMID: 11069776
  127. Koon, H.W.; Zhao, D.; Na, X.; Moyer, M.P.; Pothoulakis, C. Metalloproteinases and transforming growth factor-alpha mediate substance P-induced mitogen-activated protein kinase activation and proliferation in human colonocytes. J. Biol. Chem., 2004, 279(44), 45519-45527. doi: 10.1074/jbc.M408523200 PMID: 15319441
  128. Willert, K.; Nusse, R. Wnt proteins. Cold Spring Harb. Perspect. Biol., 2012, 4(9), a007864. doi: 10.1101/cshperspect.a007864 PMID: 22952392
  129. Polakis, P. Wnt signaling and cancer. Genes Dev., 2000, 14(15), 1837-1851. doi: 10.1101/gad.14.15.1837 PMID: 10921899
  130. Barker, N.; Clevers, H. Catenins, Wnt signaling and cancer. BioEssays, 2000, 22(11), 961-965. doi: 10.1002/1521-1878(200011)22:113.0.CO;2-T PMID: 11056471
  131. Bienz, M. beta-Catenin: a pivot between cell adhesion and Wnt signalling. Curr. Biol., 2005, 15(2), R64-R67. doi: 10.1016/j.cub.2004.12.058 PMID: 15668160
  132. DeBruine, Z.J.; Ke, J.; Harikumar, K.G.; Gu, X.; Borowsky, P.; Williams, B.O.; Xu, W.; Miller, L.J.; Xu, H.E.; Melcher, K. Wnt5a promotes Frizzled-4 signalosome assembly by stabilizing cysteine-rich domain dimerization. Genes Dev., 2017, 31(9), 916-926. doi: 10.1101/gad.298331.117 PMID: 28546512
  133. Voronkov, A.; Krauss, S. Wnt/beta-catenin signaling and small molecule inhibitors. Curr. Pharm. Des., 2013, 19(4), 634-664. doi: 10.2174/138161213804581837 PMID: 23016862
  134. Mehta, S.; Hingole, S.; Chaudhary, V. The emerging mechanisms of Wnt secretion and signaling in development. Front. Cell Dev. Biol., 2021, 9, 714746. doi: 10.3389/fcell.2021.714746 PMID: 34485301
  135. Corda, G.; Sala, A. Non-canonical WNT/PCP signalling in cancer: Fzd6 takes centre stage. Oncogenesis, 2017, 6(7), e364. doi: 10.1038/oncsis.2017.69 PMID: 28737757
  136. Janda, C.Y.; Waghray, D.; Levin, A.M.; Thomas, C.; Garcia, K.C. Structural basis of Wnt recognition by Frizzled. Science, 2012, 337(6090), 59-64. doi: 10.1126/science.1222879 PMID: 22653731
  137. Ahn, V.E.; Chu, M.L.H.; Choi, H.J.; Tran, D.; Abo, A.; Weis, W.I. Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Dev. Cell, 2011, 21(5), 862-873. doi: 10.1016/j.devcel.2011.09.003 PMID: 22000856
  138. Huang, X.; Wang, G.; Wu, Y.; Du, Z. The structure of full-length human CTNNBL1 reveals a distinct member of the armadillo-repeat protein family. Acta Crystallogr. D Biol. Crystallogr., 2013, 69(8), 1598-1608. doi: 10.1107/S0907444913011360 PMID: 23897482
  139. Brembeck, F.H.; Schwarz-Romond, T.; Bakkers, J.; Wilhelm, S.; Hammerschmidt, M.; Birchmeier, W. Essential role of BCL9-2 in the switch between β-catenin’s adhesive and transcriptional functions. Genes Dev., 2004, 18(18), 2225-2230. doi: 10.1101/gad.317604 PMID: 15371335
  140. Katoh, M.; Katoh, M. WNT signaling and cancer stemness. Essays Biochem., 2022, 66(4), 319-331. doi: 10.1042/EBC20220016 PMID: 35837811
  141. Pai, S.G.; Carneiro, B.A.; Mota, J.M.; Costa, R.; Leite, C.A.; Barroso-Sousa, R.; Kaplan, J.B.; Chae, Y.K.; Giles, F.J. Wnt/beta-catenin pathway: Modulating anticancer immune response. J. Hematol. Oncol., 2017, 10(1), 101-106. doi: 10.1186/s13045-017-0471-6 PMID: 28476164
  142. Taciak, B.; Pruszynska, I.; Kiraga, L.; Bialasek, M.; Krol, M. Wnt signaling pathway in development and cancer. J. Physiol. Pharmacol., 2018, 69(2) doi: 10.26402/jpp.2018.2.07 PMID: 29980141
  143. Sha, Y.L.; Liu, S.; Yan, W.W.; Dong, B. Wnt/β-catenin signaling as a useful therapeutic target in hepatoblastoma. Biosci. Rep., 2019, 39(9), BSR20192466. doi: 10.1042/BSR20192466 PMID: 31511432
  144. Krishnamurthy, N.; Kurzrock, R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat. Rev., 2018, 62, 50-60. doi: 10.1016/j.ctrv.2017.11.002 PMID: 29169144
  145. Javid, H.; Mohammadi, F.; Zahiri, E.; Hashemy, S.I. The emerging role of substance P/neurokinin-1 receptor signaling pathways in growth and development of tumor cells. J. Physiol. Biochem., 2019, 75(4), 415-421. doi: 10.1007/s13105-019-00697-1 PMID: 31372898
  146. Hong, H.S.; Lee, J.; Lee, E.; Kwon, Y.S.; Lee, E.; Ahn, W.; Jiang, M.H.; Kim, J.C.; Son, Y. A new role of substance P as an injury-inducible messenger for mobilization of CD29+ stromal-like cells. Nat. Med., 2009, 15(4), 425-435. doi: 10.1038/nm.1909 PMID: 19270709
  147. Garnier, A.; Vykoukal, J.; Hubertus, J.; Alt, E.; Von Schweinitz, D.; Kappler, R.; Berger, M.; Ilmer, M. Targeting the neurokinin-1 receptor inhibits growth of human colon cancer cells. Int. J. Oncol., 2015, 47(1), 151-160. doi: 10.3892/ijo.2015.3016 PMID: 25998227
  148. Niu, X.L.; Hou, J.F.; Li, J.X. The NK1 receptor antagonist NKP608 inhibits proliferation of human colorectal cancer cells via Wnt signaling pathway. Biol. Res., 2018, 51(1), 14-x. doi: 10.1186/s40659-018-0163-x PMID: 29843798
  149. Ilmer, M.; Garnier, A.; Vykoukal, J.; Alt, E.; von Schweinitz, D.; Kappler, R.; Berger, M. Targeting the neurokinin-1 receptor compromises canonical Wnt signaling in hepatoblastoma. Mol. Cancer Ther., 2015, 14(12), 2712-2721. doi: 10.1158/1535-7163.MCT-15-0206 PMID: 26516161
  150. Mei, G.; Zou, Z.; Fu, S.; Xia, L.; Zhou, J.; Zhang, Y.; Tuo, Y.; Wang, Z.; Jin, D. Substance P activates the Wnt signal transduction pathway and enhances the differentiation of mouse preosteoblastic MC3T3-E1 cells. Int. J. Mol. Sci., 2014, 15(4), 6224-6240. doi: 10.3390/ijms15046224 PMID: 24733069
  151. Zhou, J.; Ling, J.; Song, H.; Lv, B.; Wang, L.; Shang, J.; Wang, Y.; Chang, C.; Ping, F.; Qian, J. Neurokinin-1 receptor is a novel positive regulator of Wnt/β-catenin signaling in melanogenesis. Oncotarget, 2016, 7(49), 81268-81280. doi: 10.18632/oncotarget.13222 PMID: 27835606
  152. Manning, B.D.; Toker, A. Toker, A. AKT/PKB signaling: Navigating the network. Cell, 2017, 169(3), 381-405. doi: 10.1016/j.cell.2017.04.001 PMID: 28431241
  153. Xie, Y.; Shi, X.; Sheng, K.; Han, G.; Li, W.; Zhao, Q.; Jiang, B.; Feng, J.; Li, J.; Gu, Y. PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review). Mol. Med. Rep., 2018, 19(2), 783-791. doi: 10.3892/mmr.2018.9713 PMID: 30535469
  154. Akbarzadeh, M.; Mihanfar, A.; Akbarzadeh, S.; Yousefi, B.; Majidinia, M. Crosstalk between miRNA and PI3K/AKT/mTOR signaling pathway in cancer. Life Sci., 2021, 285, 119984. doi: 10.1016/j.lfs.2021.119984 PMID: 34592229
  155. Nussinov, R.; Zhang, M.; Tsai, C.J.; Jang, H. Phosphorylation and driver mutations in PI3Kα and PTEN autoinhibition. Mol. Cancer Res., 2021, 19(4), 543-548. doi: 10.1158/1541-7786.MCR-20-0818 PMID: 33288731
  156. Lien, E.C.; Dibble, C.C.; Toker, A. PI3K signaling in cancer: Beyond AKT. Curr. Opin. Cell Biol., 2017, 45, 62-71. doi: 10.1016/j.ceb.2017.02.007 PMID: 28343126
  157. Carnero, A. The PKB/AKT pathway in cancer. Curr. Pharm. Des., 2010, 16(1), 34-44. doi: 10.2174/138161210789941865 PMID: 20214616
  158. Peng, Y.; Wang, Y.; Zhou, C.; Mei, W.; Zeng, C. PI3K/Akt/mTOR pathway and its role in cancer therapeutics: Are we making headway? Front. Oncol., 2022, 12, 819128. doi: 10.3389/fonc.2022.819128 PMID: 35402264
  159. Huang, R.; Dai, Q.; Yang, R.; Duan, Y.; Zhao, Q.; Haybaeck, J.; Yang, Z. Review: PI3K/AKT/mTOR signaling pathway and its regulated eukaryotic translation initiation factors may be a potential therapeutic target in esophageal squamous cell carcinoma. Front. Oncol., 2022, 12, 817916. doi: 10.3389/fonc.2022.817916 PMID: 35574327
  160. McKenna, M.; Balasuriya, N.; Zhong, S.; Li, S.S.C.; O’Donoghue, P. Phospho-form specific substrates of protein kinase B (AKT1). Front. Bioeng. Biotechnol., 2021, 8, 619252. doi: 10.3389/fbioe.2020.619252 PMID: 33614606
  161. Ediriweera, M.K.; Tennekoon, K.H.; Samarakoon, S.R. Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance. Semin. Cancer Biol., 2019, 59, 147-160. doi: 10.1016/j.semcancer.2019.05.012 PMID: 31128298
  162. Fattahi, S.; Amjadi-Moheb, F.; Tabaripour, R.; Ashrafi, G.H.; Akhavan-Niaki, H. PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond. Life Sci., 2020, 262, 118513. doi: 10.1016/j.lfs.2020.118513 PMID: 33011222
  163. Nepstad, I.; Hatfield, K.J.; Grønningsæter, I.S.; Reikvam, H. The PI3K-Akt-mTOR signaling pathway in human acute myeloid leukemia (AML) cells. Int. J. Mol. Sci., 2020, 21(8), 2907. doi: 10.3390/ijms21082907 PMID: 32326335
  164. Zou, Z.; Tao, T.; Li, H.; Zhu, X. mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges. Cell Biosci., 2020, 10(1), 31. doi: 10.1186/s13578-020-00396-1 PMID: 32175074
  165. Iksen; Pothongsrisit, S.; Pongrakhananon, V. Targeting the PI3K/AKT/mTOR signaling pathway in lung cancer: An update regarding potential drugs and natural products. Molecules, 2021, 26(13), 4100. doi: 10.3390/molecules26134100 PMID: 34279440
  166. Stefani, C.; Miricescu, D.; Stanescu-Spinu, I.I.; Nica, R.I.; Greabu, M.; Totan, A.R.; Jinga, M. Growth factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis: Where are we now? Int. J. Mol. Sci., 2021, 22(19), 10260. doi: 10.3390/ijms221910260 PMID: 34638601
  167. Miricescu, D.; Totan, A.; Stanescu-Spinu, I.I.; Badoiu, S.C.; Stefani, C.; Greabu, M. PI3K/AKT/mTOR signaling pathway in breast cancer: From molecular landscape to clinical aspects. Int. J. Mol. Sci., 2020, 22(1), 173. doi: 10.3390/ijms22010173 PMID: 33375317
  168. Sun, K.; Luo, J.; Guo, J.; Yao, X.; Jing, X.; Guo, F. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: A narrative review. Osteoarthritis Cartilage, 2020, 28(4), 400-409. doi: 10.1016/j.joca.2020.02.027 PMID: 32081707
  169. Yang, L.; Zhang, Z.; Wang, D.; Jiang, Y.; Liu, Y. Targeting mTOR signaling in type 2 diabetes mellitus and diabetes complications. Curr. Drug Targets, 2022, 23(7), 692-710. doi: 10.2174/1389450123666220111115528 PMID: 35021971
  170. Ramasubbu, K. Devi Rajeswari, V. Impairment of insulin signaling pathway PI3K/Akt/mTOR and insulin resistance induced AGEs on diabetes mellitus and neurodegenerative diseases: A perspective review. Mol. Cell Biochem., 2023, 478(6), 1307-1324. doi: 10.1007/s11010-022-04587-x PMID: 36308670
  171. Xu, Q.; Fitzsimmons, B.; Steinauer, J.; Neill, A.O.; Newton, A.C.; Hua, X.Y.; Yaksh, T.L. Spinal phosphinositide 3-kinase-Akt-mammalian target of rapamycin signaling cascades in inflammation-induced hyperalgesia. J. Neurosci., 2011, 31(6), 2113-2124. doi: 10.1523/JNEUROSCI.2139-10.2011 PMID: 21307248
  172. Lasagni Vitar, R.; Triani, F.; Barbariga, M.; Fonteyne, P.; Rama, P.; Ferrari, G. Substance P/neurokinin-1 receptor pathway blockade ameliorates limbal stem cell deficiency by modulating mTOR pathway and preventing cell senescence. Stem Cell Rep., 2022, 17(4), 849-863. doi: 10.1016/j.stemcr.2022.02.012 PMID: 35334220
  173. Lim, J.E.; Chung, E.; Son, Y. A neuropeptide, Substance-P, directly induces tissue-repairing M2 like macrophages by activating the PI3K/Akt/mTOR pathway even in the presence of IFNγ. Sci. Rep., 2017, 7(1), 9417. doi: 10.1038/s41598-017-09639-7 PMID: 28842601
  174. Wang, J.G.; Yu, J.; Hu, J.L.; Yang, W.L.; Ren, H.; Ding, D.; Zhang, L.; Liu, X.P. Neurokinin-1 activation affects EGFR related signal transduction in triple negative breast cancer. Cell. Signal., 2015, 27(7), 1315-1324. doi: 10.1016/j.cellsig.2015.03.015 PMID: 25817575
  175. Akazawa, T.; Kwatra, S.G.; Goldsmith, L.E.; Richardson, M.D.; Cox, E.A.; Sampson, J.H.; Kwatra, M.M. A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas. J. Neurochem., 2009, 109(4), 1079-1086. doi: 10.1111/j.1471-4159.2009.06032.x PMID: 19519779
  176. Kolorz, J.; Demir, S.; Gottschlich, A.; Beirith, I.; Ilmer, M.; Lüthy, D.; Walz, C.; Dorostkar, M.M.; Magg, T.; Hauck, F.; von Schweinitz, D.; Kobold, S.; Kappler, R.; Berger, M. The neurokinin-1 receptor is a target in pediatric rhabdoid tumors. Curr. Oncol., 2021, 29(1), 94-110. doi: 10.3390/curroncol29010008 PMID: 35049682
  177. Fong, T.M.; Anderson, S.A.; Yu, H.; Huang, R.R.; Strader, C.D. Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor. Mol. Pharmacol., 1992, 41(1), 24-30. PMID: 1310144
  178. Baker, S.J.; Morris, J.L.; Gibbins, I.L. Cloning of a C-terminally truncated NK-1 receptor from guinea-pig nervous system. Brain Res. Mol. Brain Res., 2003, 111(1-2), 136-147. doi: 10.1016/S0169-328X(03)00002-0 PMID: 12654513
  179. Mantyh, P.W.; Rogers, S.D.; Ghilardi, J.R.; Maggio, J.E.; Mantyh, C.R.; Vigna, S.R. Differential expression of two isoforms of the neurokinin-1 (substance P) receptor in vivo. Brain Res., 1996, 719(1-2), 8-13. doi: 10.1016/0006-8993(96)00050-9 PMID: 8782857
  180. Page, N.M. Characterization of the gene structures, precursor processing and pharmacology of the endokinin peptides. Vascul. Pharmacol., 2006, 45(4), 200-208. doi: 10.1016/j.vph.2005.08.028 PMID: 16931167
  181. Satake, H.; Kawada, T. Overview of the primary structure, tissue-distribution, and functions of tachykinins and their receptors. Curr. Drug Targets, 2006, 7(8), 963-974. doi: 10.2174/138945006778019273 PMID: 16918325
  182. Douglas, S.D.; Leeman, S.E. Neurokinin-1 receptor: Functional significance in the immune system in reference to selected infections and inflammation. Ann. N. Y. Acad. Sci., 2011, 1217(1), 83-95. doi: 10.1111/j.1749-6632.2010.05826.x PMID: 21091716
  183. Tuluc, F.; Meshki, J.; Spitsin, S.; Douglas, S.D. HIV infection of macrophages is enhanced in the presence of increased expression of CD163 induced by substance P. J. Leukoc. Biol., 2014, 96(1), 143-150. doi: 10.1189/jlb.4AB0813-434RR PMID: 24577568
  184. Li, H.; Leeman, S.E.; Slack, B.E.; Hauser, G.; Saltsman, W.S.; Krause, J.E.; Blusztajn, J.K.; Boyd, N.D. A substance P (neurokinin-1) receptor mutant carboxyl-terminally truncated to resemble a naturally occurring receptor isoform displays enhanced responsiveness and resistance to desensitization. Proc. Natl. Acad. Sci. USA, 1997, 94(17), 9475-9480. doi: 10.1073/pnas.94.17.9475 PMID: 9256507
  185. Richardson, M.D.; Balius, A.M.; Yamaguchi, K.; Freilich, E.R.; Barak, L.S.; Kwatra, M.M. Human substance P receptor lacking the C-terminal domain remains competent to desensitize and internalize. J. Neurochem., 2003, 84(4), 854-863. doi: 10.1046/j.1471-4159.2003.01577.x PMID: 12562528
  186. Déry, O.; Defea, K.A.; Bunnett, N.W. Protein kinase C-mediated desensitization of the neurokinin 1 receptor. Am. J. Physiol. Cell Physiol., 2001, 280(5), C1097-C1106. doi: 10.1152/ajpcell.2001.280.5.C1097 PMID: 11287322
  187. Gao, X.; Frakich, N.; Filippini, P.; Edwards, L.J.; Vinkemeier, U.; Gran, B.; Tanasescu, R.; Bayraktutan, U.; Colombo, S.; Constantinescu, C.S. Effects of substance P on human cerebral microvascular endothelial cell line hCMEC/D3 are mediated exclusively through a truncated NK-1 receptor and depend on cell confluence. Neuropeptides, 2022, 95, 102265. doi: 10.1016/j.npep.2022.102265 PMID: 35696961
  188. Lai, J.P.; Lai, S.; Tuluc, F.; Tansky, M.F.; Kilpatrick, L.E.; Leeman, S.E.; Douglas, S.D. Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor. Proc. Natl. Acad. Sci., 2008, 105(34), 12605-12610. doi: 10.1073/pnas.0806632105 PMID: 18713853
  189. Muñoz, M.F.; Argüelles, S.; Rosso, M.; Medina, R.; Coveñas, R.; Ayala, A.; Muñoz, M. The neurokinin-1 receptor is essential for the viability of human glioma cells: A possible target for treating glioblastoma. BioMed Res. Int., 2022, 2022, 1-13. doi: 10.1155/2022/6291504 PMID: 35434136
  190. Molinos-Quintana, A.; Trujillo-Hacha, P.; Piruat, J.I.; Bejarano-García, J.A.; García-Guerrero, E.; Pérez-Simón, J.A.; Muñoz, M. Human acute myeloid leukemia cells express Neurokinin-1 receptor, which is involved in the antileukemic effect of neurokinin-1 receptor antagonists. Invest. New Drugs, 2019, 37(1), 17-26. doi: 10.1007/s10637-018-0607-8 PMID: 29721755
  191. Mozafari, M.; Ebrahimi, S.; Darban, R.A.; Hashemy, S.I. Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer. Mol. Biol. Rep., 2022, 49(2), 1067-1076. doi: 10.1007/s11033-021-06928-3 PMID: 34766230
  192. Zhou, Y.; Wang, M.; Tong, Y.; Liu, X.; Zhang, L.; Dong, D.; Shao, J.; Zhou, Y. miR-206 promotes cancer progression by targeting full-length neurokinin-1 receptor in breast cancer. Technol. Cancer Res. Treat., 2019, 18 doi: 10.1177/1533033819875168 PMID: 31506061
  193. Liu, X.; Zhang, L.; Tong, Y.; Yu, M.; Wang, M.; Dong, D.; Shao, J.; Zhang, F.; Niu, R.; Zhou, Y. MicroRNA-22 inhibits proliferation, invasion and metastasis of breast cancer cells through targeting truncated neurokinin-1 receptor and ERα. Life Sci., 2019, 217, 57-69. doi: 10.1016/j.lfs.2018.11.057 PMID: 30502362
  194. Berger, M.; Neth, O.; Ilmer, M.; Garnier, A.; Salinas-Martín, M.V.; de Agustín Asencio, J.C.; von Schweinitz, D.; Kappler, R.; Muñoz, M. Hepatoblastoma cells express truncated neurokinin-1 receptor and can be growth inhibited by aprepitant in vitro and in vivo. J. Hepatol., 2014, 60(5), 985-994. doi: 10.1016/j.jhep.2013.12.024 PMID: 24412605
  195. Pohl, A.; Kappler, R.; Mühling, J.; VON Schweinitz, D.; Berger, M. Expression of truncated neurokinin-1 receptor in childhood neuroblastoma is independent of tumor biology and stage. Anticancer Res., 2017, 37(11), 6079-6085. PMID: 29061788
  196. Gao, X.; Wang, Z. Difference in expression of two neurokinin-1 receptors in adenoma and carcinoma from patients that underwent radical surgery for colorectal carcinoma. Oncol. Lett., 2017, 14(3), 3729-3733. doi: 10.3892/ol.2017.6588 PMID: 28927139
  197. Gillespie, E.; Leeman, S.E.; Watts, L.A.; Coukos, J.A.; O’Brien, M.J.; Cerda, S.R.; Farraye, F.A.; Stucchi, A.F.; Becker, J.M. Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer. Proc. Natl. Acad. Sci. USA, 2011, 108(42), 17420-17425. doi: 10.1073/pnas.1114275108 PMID: 21969570
  198. Patel, H.J.; Ramkissoon, S.H.; Patel, P.S.; Rameshwar, P. Transformation of breast cells by truncated neurokinin-1 receptor is secondary to activation by preprotachykinin-A peptides. Proc. Natl. Acad. Sci. USA, 2005, 102(48), 17436-17441. doi: 10.1073/pnas.0506351102 PMID: 16291810
  199. Nahas, G.R.; Murthy, R.G.; Patel, S.A.; Ganta, T.; Greco, S.J.; Rameshwar, P. The RNA-binding protein Musashi 1 stabilizes the oncotachykinin 1 mRNA in breast cancer cells to promote cell growth. FASEB J., 2016, 30(1), 149-159. doi: 10.1096/fj.15-278770 PMID: 26373800
  200. Navarro, P.; Ramkissoon, S.H.; Shah, S.; Park, J.M.; Murthy, R.G.; Patel, S.A.; Greco, S.J.; Rameshwar, P. An indirect role for the oncomir-519b in the expression of truncated neurokinin-1 in breast cancer cells. Exp. Cell Res., 2012, 318(20), 2604-2615. doi: 10.1016/j.yexcr.2012.09.002 PMID: 22981979
  201. Ramkissoon, S.H.; Patel, P.S.; Taborga, M.; Rameshwar, P. Nuclear factor-kappaB is central to the expression of truncated neurokinin-1 receptor in breast cancer: implication for breast cancer cell quiescence within bone marrow stroma. Cancer Res., 2007, 67(4), 1653-1659. doi: 10.1158/0008-5472.CAN-06-3813 PMID: 17308106
  202. Muñoz, M.; Crespo, J.C.; Crespo, J.P.; Coveñas, R. Neurokinin-1 receptor antagonist aprepitant and radiotherapy, a successful combination therapy in a patient with lung cancer: A case report. Mol. Clin. Oncol., 2019, 11(1), 50-54. doi: 10.3892/mco.2019.1857 PMID: 31289677
  203. Muñoz, M.; Coveñas, R. Neurokinin receptor antagonism: a patent review (2014-present). Expert Opin. Ther. Pat., 2020, 30(7), 527-539. doi: 10.1080/13543776.2020.1769599 PMID: 32401556
  204. Avet, C.; Mancini, A.; Breton, B.; Le Gouill, C.; Hauser, A.S.; Normand, C.; Kobayashi, H.; Gross, F.; Hogue, M.; Lukasheva, V.; St-Onge, S.; Carrier, M.; Héroux, M.; Morissette, S.; Fauman, E.B.; Fortin, J.P.; Schann, S.; Leroy, X.; Gloriam, D.E.; Bouvier, M. Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs. eLife, 2022, 11, e74101. doi: 10.7554/eLife.74101 PMID: 35302493
  205. Wang, F.I.; Ding, G.; Ng, G.S.; Dixon, S.J.; Chidiac, P. Luciferase-based GloSensor™ cAMP assay: Temperature optimization and application to cell-based kinetic studies. Methods, 2022, 203, 249-258. doi: 10.1016/j.ymeth.2021.10.009 PMID: 34737032
  206. Tei, R.; Baskin, J.M. Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling. J. Biol. Chem., 2022, 298(4), 101810. doi: 10.1016/j.jbc.2022.101810 PMID: 35276134
  207. Leo, K.T.; Chou, C.L.; Yang, C.R.; Park, E.; Raghuram, V.; Knepper, M.A. Bayesian analysis of dynamic phosphoproteomic data identifies protein kinases mediating GPCR responses. Cell Commun. Signal., 2022, 20(1), 80-86. doi: 10.1186/s12964-022-00892-6 PMID: 35659261
  208. Hijazi, M.; Smith, R.; Rajeeve, V.; Bessant, C.; Cutillas, P.R. Reconstructing kinase network topologies from phosphoproteomics data reveals cancer-associated rewiring. Nat. Biotechnol., 2020, 38(4), 493-502. doi: 10.1038/s41587-019-0391-9 PMID: 31959955
  209. Michel, M.C.; Charlton, S.J. Biased agonism in drug discovery-is it too soon to choose a path? Mol. Pharmacol., 2018, 93(4), 259-265. doi: 10.1124/mol.117.110890 PMID: 29326242
  210. Recio, R.; Lerena, P.; Pozo, E.; Calderón-Montaño, J.M.; Burgos-Morón, E.; López-Lázaro, M.; Valdivia, V.; Pernia Leal, M.; Mouillac, B.; Organero, J.Á.; Khiar, N.; Fernández, I. Carbohydrate-based NK1R antagonists with broad-spectrum anticancer activity. J. Med. Chem., 2021, 64(14), 10350-10370. doi: 10.1021/acs.jmedchem.1c00793 PMID: 34236855
  211. Paradis, J.S.; Feng, X.; Murat, B.; Jefferson, R.E.; Sokrat, B.; Szpakowska, M.; Hogue, M.; Bergkamp, N.D.; Heydenreich, F.M.; Smit, M.J.; Chevigné, A.; Bouvier, M.; Barth, P. Computationally designed GPCR quaternary structures bias signaling pathway activation. Nat. Commun., 2022, 13(1), 6826. doi: 10.1038/s41467-022-34382-7 PMID: 36369272
  212. Morales-Pastor, A.; Nerín-Fonz, F.; Aranda-García, D.; Dieguez-Eceolaza, M.; Medel-Lacruz, B.; Torrens-Fontanals, M.; Peralta-García, A.; Selent, J. In silico study of allosteric communication networks in GPCR signaling bias. Int. J. Mol. Sci., 2022, 23(14), 7809. doi: 10.3390/ijms23147809 PMID: 35887157
  213. Ebrahimi, S.; Mirzavi, F.; Hashemy, S.I.; Khaleghi Ghadiri, M.; Stummer, W.; Gorji, A. The in vitro anti-cancer synergy of neurokinin-1 receptor antagonist, aprepitant, and 5-aminolevulinic acid in glioblastoma. Biofactors, 2023, 49(4), 900-911. doi: 10.1002/biof.1953 PMID: 37092793
  214. Ebrahimi, S.; Erfani, B.; Alalikhan, A.; Ghorbani, H.; Farzadnia, M.; Afshari, A.R.; Mashkani, B.; Hashemy, S.I. The in vitro pro-inflammatory functions of the SP/NK1R system in prostate cancer: A focus on nuclear factor-kappa B (NF-κB) and its pro-inflammatory target genes. Appl. Biochem. Biotechnol., 2023. doi: 10.1007/s12010-023-04495-w PMID: 37093533
  215. Królicki, L.; Kunikowska, J.; Bruchertseifer, F.; Kuliński, R.; Pawlak, D.; Koziara, H.; Rola, R.; Morgenstern, A.; Merlo, A. Locoregional treatment of glioblastoma with targeted α therapy: 213 BiBi-DOTA-substance P versus 225 AcAc-DOTA-substance P-analysis of influence parameters. Clin. Nucl. Med., 2023, 48(5), 387-392. doi: 10.1097/RLU.0000000000004608 PMID: 36854309
  216. Robinson, P.; Rosso, M.; Muñoz, M. Neurokinin-1 Receptor antagonists as a potential novel therapeutic option for osteosarcoma patients. J. Clin. Med., 2023, 12(6), 2135. doi: 10.3390/jcm12062135 PMID: 36983138
  217. Suthiram, J.; Pieters, A.; Mohamed Moosa, Z.; Zeevaart, J.R.; Sathekge, M.M.; Ebenhan, T.; Anderson, R.C.; Newton, C.L. Tachykinin receptor-selectivity of the potential glioblastoma-targeted therapy, DOTA-Thi8,Met(O2)11-substance P. Int. J. Mol. Sci., 2023, 24(3), 2134. doi: 10.3390/ijms24032134 PMID: 36768456
  218. Guan, L.; Yuan, S.; Ma, J.; Liu, H.; Huang, L.; Zhang, F. Neurokinin-1 receptor is highly expressed in cervical cancer and its antagonist induces cervical cancer cell apoptosis. Eur. J. Histochem., 2023, 67(1), 3570. doi: 10.4081/ejh.2023.3570 PMID: 36629320
  219. Kant, V.; Mahapatra, P.S.; Gupta, V.; Bag, S.; Gopalakrishnan, A.; Kumar, D.; Kumar, D. Substance P, a neuropeptide, promotes wound healing via neurokinin-1 receptor. Int. J. Low. Extrem. Wounds, 2023, 22(2), 291-297. doi: 10.1177/15347346211004060 PMID: 33856252
  220. Choi, J.G.; Choi, S.R.; Kang, D.W.; Shin, H.J.; Lee, M.; Hwang, J.; Kim, H.W. Inhibition of angiotensin converting enzyme increases PKCβI isoform expression via activation of substance P and bradykinin receptors in cultured astrocytes of mice. J. Vet. Sci., 2023, 24(2), e26. doi: 10.4142/jvs.22275 PMID: 37012034
  221. Al-Keilani, M.S.; Bdeir, R.; Elstaty, R.I.; Alqudah, M.A. Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival. BMC Cancer, 2023, 23(1), 158. doi: 10.1186/s12885-023-10633-8 PMID: 36797689

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