An Insight into GPCR and G-Proteins as Cancer Drivers

Abstract

G-protein-coupled receptors (GPCRs) are the largest family of cell surface signaling receptors known to play a crucial role in various physiological functions, including tumor growth and metastasis. Various molecules such as hormones, lipids, peptides, and neurotransmitters activate GPCRs that enable the coupling of these receptors to highly specialized transducer proteins, called G-proteins, and initiate multiple signaling pathways. Integration of these intricate networks of signaling cascades leads to numerous biochemical responses involved in diverse pathophysiological activities, including cancer development. While several studies indicate the role of GPCRs in controlling various aspects of cancer progression such as tumor growth, invasion, migration, survival, and metastasis through its aberrant overexpression, mutations, or increased release of agonists, the explicit mechanisms of the involvement of GPCRs in cancer progression is still puzzling. This review provides an insight into the various responses mediated by GPCRs in the development of cancers, the molecular mechanisms involved and the novel pharmacological approaches currently preferred for the treatment of cancer. Thus, these findings extend the knowledge of GPCRs in cancer cells and help in the identification of therapeutics for cancer patients.

Keywords: G-protein; GPCR; GPCR signaling; cancer.

Figure 1

GPCR-mediated cell signaling pathways associated with cancer. Upon ligand binding, GPCR activates several downstream signaling pathways, including secondary such as GEFs for Rho, MAPKs, PI3Ks, along with their numerous cytosolic and nuclear targets. These receptor-mediated signaling cascades initiate various pathophysiological processes such as cell growth, survival, differentiation, tumor cell initiation, progression, and metastasis. Refer to the text for a detailed mechanism. Apdated from Lappano et al. [21].