Role of G-Protein Coupled Receptors in Cancer Research and Drug Discovery

Authors(2) :-Mahin Ghorbani, Hamed Karimi

G-Protein Coupled Receptors as the largest class of cell surface signaling proteins are widely considered in drug discovery programs as therapeutic drug targets; their contribution in drug discovery process is because of their critical role in many physiological functions and their link with emerging different types of diseases including cancer development and cancer metastasis. Their association to hereditary diseases, made them important for examination as novel targets too. As they constitute the target of 50% of the available therapeutic agents in the market, they are still most attractive potential targets for developing new drugs especially anti-cancer drugs. Their structure function relationship have been made them a powerful basis for screening a large number of pharmaceutical products. In this paper we purpose to review significant role of the GPCRs in cancer development and drug discovery along with the information regarding their structure, classification and recent studies and findings about their position as drug targets. This review provides scientists for development of favorable opportunities for drug discovery in cancer research including prevention and diagnosis and treatment.

Authors and Affiliations

Mahin Ghorbani
Department of Biotechnology, Fergusson College, F.C. Road, Pune, Maharashtra, India
Hamed Karimi
Department of Information Technology, Payam Noor University of Farokh-shahr, Farokh-shahr, Chaharmahl va bakhtiari, Iran

Corporation of G-Protein Coupled Receptors, Drug Target, Drug Discovery, Associated Disesaeas, Cancer

  1. Marinissen MJ, Gutkind JS: G-Protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22: 368-376, 2001
  2. Rastogi.S. C., Rastogi P and Mendiratta N., 2008. Bioinformatics Methods and Applications: Genomics.Proteomics And Drug Discovery PHI Learning Pvt. Ltd
  3. Alkhalfioui F, Magnin T, Wagner R: From purified GPCRs to drug discovery: the promise of protein-based methodologies. Curr Opin Pharmacol 9: 629-635, 2009.
  4. Schoneberg T, Schulz A, Biebermann H, Hermsdorf T, Rompler H, Sangkuhl K: Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacol Ther 104: 173-206, 2004.
  5. Eo HS, Choi JP, Noh SJ, Hur CG, Kim W: A combined approach for the classification of G-protein-coupled receptors and its application to detect GPCR splice variants. Comput Biol Chem 31: 246-256, 2007.
  6. Kanazawa T, Misawa K, Misawa Y, Uehara T, Fukushima H, Kusaka G, Maruta M, Carey TE.G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer? Toxins (Basel). 2015 Aug 5;7(8):2959-2984.
  7. Santolla MF, De Francesco EM, Lappano R1, Rosano C, Abonante S3, Maggiolini M.Niacin activates the G protein estrogen receptor (GPER)-mediated signalling. Cell Signal. 2014 Jul;26(7):1466-75.
  8. Ji-yuan Sun :GPCR-CARMA3-NF-kappaB signaling axis: A novel drug target for cancer therapy.Clinical Oncology and Cancer Research June 2010, Volume 7, Issue 3, pp 159-168.
  9. Gao Y, Kitagawa K, Hiramatsu Y, Kikuchi H, Isobe T, Shimada M, Uchida C, Hattori T, Oda T, Nakayama K, Nakayama KI, Tanaka T, Konno H, Kitagawa M:Up-regulation of GPR48 induced by down-regulation of p27/Kip1 enhances carcinoma cell invasiveness and metastasis. Cancer Res 66: 11623-11631, 2006.
  10. Gugger M,White R, Song S, Waser B, Cescato R, Riviere P, Reubi JC: GPR87 is an overexpressed G-protein-coupled receptor in squamous cell carcinoma of the lung. Dis Markers 24: 41-50, 2008.
  11. Yamamoto Y, Sakamoto M, Fujii G, Tsuiji H, Kenetaka K, Asaka M, Hirohashi : Overexpression of orphan G-protein-coupled receptor, GPR49, in human hepatocellular carcinomas with beta-catenin mutations. Hepatology 37: 528-533, 2003.
  12. Shashidhar S, Lorente G, Nagavarapu U, Nelson A, Kuo J, Cummins J, Nikolich K, Urfer R, Foehr ED: GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion. Oncogene 24: 1673-1682, 2005
  13. Jinhua Wu, Na Xie,*Xia Zhao, Edouard C. Nice and Canhua Huang Dissection of Aberrant GPCR Signaling in Tumorigenesis - A Systems Biology Approach.Cancer Genomics and Proteomics January-February 2012 vol. 9 no. 1 37-50
  14. Weigle B, Fuessel S, Ebner R, Temme A, Schmitz M, Schwind S, Kiessling A, Rieger MA, Meye A, Bachmann M, Wirth MP, Rieber EP: D-GPCR: a novel putative G protein-coupled receptor overexpressed in prostate cancer and prostate. Biochem Biophys Res Commun 322: 239-249, 2004.
  15. Weng J, Wang J, Hu X, Wang F,Ittmann M,: PSGR2, a novel G-protein coupled receptor, is overexpressed in human prostate cancer. Int J Cancer 118: 1471-1480, 2006.
  16. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC:Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 366: 575-580, 1993.
  17. Mihai R, Stevens J, McKinney C, Ibrahim NB: Expression of the calcium receptor in human breast cancer-a potential new marker predicting the risk of bone metastases. Eur J Surg Oncol 32: 511-515, 2006.
  18. Filardo EJ, Graeber CT, Quinn JA, Resnick MB, Giri D, DeLellis RA, Steinhoff MM, Sabo E: Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clin Cancer Res 12: 6359-6366, 2006.
  19. Pandey DP, Lappano R, Albanito L, Madeo A, Maggiolini M,Picard D: Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J 28: 523-532, 2009.
  20. Xie F, Liu H, Zhu YH, Qin YR, Dai Y, Zeng T, Chen L, Nie C, Tang H, Li Y, Fu L, Guan X: Overexpression of GPR39 contributes to malignant development of human esophageal squamous cell carcinoma. BMC Cancer 11: 86, 2011.
  21. Liu Y, Wada R, Yamashita T,Mi Y, Deng CX, Hobson JP, Rosenfeldt HM, Nava VE, Chae SS, Lee MJ, Liu CH, Hla T, Spiegel S, Proia RL: Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest 106: 951-961, 2000.
  22. Mills GB, Moolenaar WH: The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 3: 582-591, 2003.
  23. Rivera-Lopez CM, Tucker AL, Lynch KR: Lysophosphatidic acid (LPA) and angiogenesis. Angiogenesis 11: 301-310, 2008.
  24. Jonkers J, Moolenaar WH: Mammary tumorigenesis through LPA receptor signaling. Cancer Cell 15: 457-459, 2009.
  25. Caunt M, Huang YQ, Brooks PC, Karpatkin S: Thrombin induces neoangiogenesis in the chick chorioallantoic membrane. J Thromb Haemost 1: 2097-2102, 2003.
  26. Bussolino F, Arese M, Montrucchio G, Barra L, Primo L, Benelli R, Sanavio F, Aglietta M, Ghigo D, Rola-Pleszczynski MR: Platelet-activating factor produced in vitro by Kaposi’s sarcoma cells induces and sustains in vivo angiogenesis. J Clin Invest 96: 940-952, 1995.
  27. Montrucchio G, Lupia E, Battaglia E, Del Sorbo L, Boccellino M, Biancone L, Emanuelli G, Camussi G: Platelet-activating factor enhances vascular endothelial growth factor-induced endothelial cell motility and neoangiogenesis in a murine matrigel model. Arterioscler Thromb Vasc Biol 20: 80-88, 2000.
  28. Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H, Kuwano M: Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol 17: 4015-4023, 1997.
  29. Carmeliet P, Jain RK: Angiogenesis in cancer and other diseases. Nature 407: 249-257, 2000.
  30. Moore BB, Keane MP, Addison CL, Arenberg DA, Strieter RM: CXC chemokine modulation of angiogenesis: the importance of balance between angiogenic and angiostatic members of the family. J Investig Med 46: 113-120, 1998.
  31. Ghorbani M, Karimi H, 'Ion Channels Association with Diseases and their Role as Therapeutic Targets in Drug Discovery', International Journal of Scientific Research in Science and Technology(IJSRST), 1(3):65-69,July-August 2015.
  32. Ghorbani M and Karimi H. Cyclin-Dependent Kinases as valid targets for cancer treatment. Journal of Pharmacy Research 2015,9(6),377-382
  33. Ghorbani M, Karimi H, 'Role of Aquaporins in Diseases and Drug Discovery', International Journal of Scientific Research in Science and Technology (IJSRST), 1(3):60-64, July-August 2015.

Publication Details

Published in : Volume 1 | Issue 3 | July-August 2015
Date of Publication : 2015-08-25
License:  This work is licensed under a Creative Commons Attribution 4.0 International License.
Page(s) : 122-126
Manuscript Number : IJSRST151321
Publisher : Technoscience Academy

Print ISSN : 2395-6011, Online ISSN : 2395-602X

Cite This Article :

Mahin Ghorbani, Hamed Karimi, " Role of G-Protein Coupled Receptors in Cancer Research and Drug Discovery", International Journal of Scientific Research in Science and Technology(IJSRST), Print ISSN : 2395-6011, Online ISSN : 2395-602X, Volume 1, Issue 3, pp.122-126 , July-August-2015.
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