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.

The Orexin-A/OX1R System Induces Cell Death in Pancreatic Cancer Cells Resistant to Gemcitabine and Nab-Paclitaxel Treatment

“…It is well known that GPCRs, identified as the largest cell surface receptor family that is the most common therapeutic target encompassing about 40% of FDA-approved molecules, represent an innovative target in cancer ( 26 ). It is common that GPCRs emerged as key targets in tumor growth and/or metastasis associated to their overexpression/underexpression in cancer cells and also their abilities to stimulate/inhibit proliferation or inversely stimulate/inhibit apoptosis ( 27 ). Among this large family, we have demonstrated in 2011 that OX1R, but not OX2R, was ectopically expressed in colon cancer whatever its location and/or grade of development ( 15 ).…”

DNA Methylation-Specific Analysis of G Protein-Coupled Receptor-Related Genes in Pan-Cancer

“…GPCR dysregulation is related to a variety of human diseases and disorder [ 22 ]. Novel GPCRs that are changed in cancer have been discovered in genome-wide comprehensive investigations of different human malignancies.…”

Plasmalogenic Lipid Analogs as Platelet-Activating Factor Antagonists: A Potential Novel Class of Anti-inflammatory Compounds

“…Human and guinea pig PAFRs consist of a single polypeptide chain composed of 342 amino acids with seven transmembrane domains, with the characteristics of G-protein coupled receptors (GPCRs) superfamily ( Chaudhary and Kim, 2021 ; Ishii et al, 2002 ). GPCRs are the largest and most diverse group of membrane receptors in the eukaryotes.…”