Format

Send to

Choose Destination
J Biol Chem. 2019 Jun 5. pii: jbc.REV119.005601. doi: 10.1074/jbc.REV119.005601. [Epub ahead of print]

Illuminating the Onco-GPCRome: Novel G protein-coupled receptor-driven oncocrine networks and targets for cancer immunotherapy.

Author information

1
Department of Pharmacology, UCSD Moores Cancer Center, United States.
2
Department of Medicine, UCSD Moores Cancer Center, United States.
3
Japan Oncology Science Unit, MSD K.K, Japan.
4
Pediatrics, Department of Pediatrics, UCSD School of Medicine, United States.
5
Heidelberg University, Germany.
6
Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.
7
Department of Medicine, UCSD Moores Cancer Center.
8
Pharmacology, Department of Pharmacology, UCSD Moores Cancer Center, United States.

Abstract

G protein-coupled receptors (GPCRs) are the largest gene family of cell membrane-associated molecules mediating signal transmission, and their involvement in key physiological functions is well established. The ability of GPCRs to regulate a vast array of fundamental biological processes, such as cardiovascular functions, immune responses, hormone and enzyme release from endocrine and exocrine glands, neurotransmission, and sensory perception (e.g. vision, odor, and taste) is largely due to the diversity of these receptors and the layers of their downstream signaling circuits. Dysregulated expression and aberrant functions of GPCRs have been linked to some of the most prevalent human diseases, which renders GPCRs one of the top targets for pharmaceutical drug development. However, the study of the role of GPCRs in tumor biology has only just begun to make headway. Recent studies have shown that GPCRs can contribute to the many facets of tumorigenesis, including proliferation, survival, angiogenesis, invasion, metastasis, therapy resistance, and immune evasion. Indeed, GPCRs are widely dysregulated in cancer and yet are underexploited in oncology. We present here a comprehensive analysis of GPCR gene expression, copy number variation, and mutational signatures inĀ  33 cancer types. We also highlight the emerging role of GPCRs as part of oncocrine networks promoting tumor growth, dissemination, and immune evasion, and stress the potential benefits of targeting GPCRs and their signaling circuits in the new era of precision medicine and cancer immunotherapies.

KEYWORDS:

Drug repurposing; G protein; G protein-coupled receptor (GPCR); Oncocrine signaling; Precision therapies; cancer; immunotherapy; signal transduction

PMID:
31171722
DOI:
10.1074/jbc.REV119.005601
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center