title: G Protein-Coupled Receptors in Cancer.
abstract: Despite the fact that G protein-coupled receptors (GPCRs) are the largest signal-conveying receptor family and mediate many physiological processes, their role in tumor biology is underappreciated. Numerous lines of evidence now associate GPCRs and their downstream signaling targets in cancer growth and development. Indeed, GPCRs control many features of tumorigenesis, including immune cell-mediated functions, proliferation, invasion and survival at the secondary site. Technological advances have further substantiated GPCR modifications in human tumors. Among these are point mutations, gene overexpression, GPCR silencing by promoter methylation and the number of gene copies. At this point, it is imperative to elucidate specific signaling pathways of "cancer driver" GPCRs. Emerging data on GPCR biology point to functional selectivity and "biased agonism"; hence, there is a diminishing enthusiasm for the concept of "one drug per GPCR target" and increasing interest in the identification of several drug options. Therefore, determining the appropriate context-dependent conformation of a functional GPCR as well as the contribution of GPCR alterations to cancer development remain significant challenges for the discovery of dominant cancer genes and the development of targeted therapeutics.
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. Rachelbar@ekmd.huji.ac.il.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bar-Shavit
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. Myriamm@hadassah.org.il.
authors.forename: Myriam
authors.initials: M
authors.lastname: Maoz
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. kancharlarn@gmail.com.
authors.forename: Arun
authors.initials: A
authors.lastname: Kancharla
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. jeetendr.nag@mail.huji.ac.il.
authors.forename: Jeetendra Kumar
authors.initials: JK
authors.lastname: Nag
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. Danyaag@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Agranovich
authors.affiliation: Department of Obstetrics and Gynecology, Shaare-Zedek Medical Center, Jerusalem 91031, Israel. sorina@szmc.org.il.
authors.forename: Sorina
authors.initials: S
authors.lastname: Grisaru-Granovsky
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. Beatrice@hadassah.org.il.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Uziely
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: CXCR4; G protein-coupled receptors (GPCRs); Hippo/YAP; LPA(1-6); PH-domain; Wnt/β-catenin; cancer; oncogenes; protease; protease-activated receptor; protease-activated receptors (PARs)