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

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

Publication date: Jun 05, 2019

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 in 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.

, Wu, Yeerna, H., Nohata, N., Chiou, J., Harismendy, O., Raimondi, F., Inoue, A., Russell, R.B., Tamayo, P., and Gutkind, J.S. Illuminating the Onco-GPCRome: Novel G protein-coupled receptor-driven oncocrine networks and targets for cancer immunotherapy. 04757. 2019 J Biol Chem.

Concepts Keywords
Angiogenesis Drug development
Cardiovascular GPR114
Endocrine Cell biology
Enzyme Cell signaling
Exocrine Glands G protein-coupled receptors
GPCR Branches of biology
Headway Immunotherapy
Hormone Immunotherapies
Immunotherapies However GPCRs tumor
Immunotherapy Tumor
Membrane Prevalent diseases
Metastasis Part oncocrine networks
Neurotransmission
Oncology
Pharmaceutical Drug
Protein
Receptor
Receptors
Sensory Perception
Stress
Tumor
Tumorigenesis

Semantics

Type Source Name
disease MESH development
gene UNIPROT THOP1
pathway BSID Release
disease DOID cancer
disease MESH cancer
pathway BSID Signal Transduction
gene UNIPROT ESR1
gene UNIPROT ERAL1
pathway BSID Gene Expression
gene UNIPROT FZD4
gene UNIPROT MRGPRX3
gene UNIPROT LPAR3
gene UNIPROT GPR151
gene UNIPROT OXER1
gene UNIPROT MRGPRX4
gene UNIPROT GPRC6A
gene UNIPROT MRGPRX1
gene UNIPROT LGR6
disease MESH metastasis
pathway BSID Angiogenesis
disease MESH tumorigenesis

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