Abstract: G protein coupled receptors (GPCRs) belong to a superfamily of cell surface receptors, which activate heterotrimeric G proteins that transduce a vast variety of extracellular stimuli, including hormones, ions, organic molecules, and light into the intracellular “effectors” to generate cellular responses. It is widely accepted that GPCR signaling pathways have emerged as the critical mediators for oncogenic signaling. Regulators of G protein signaling ( RGS) proteins are key proteins in GPCR signaling regulations. Many members in the RGS family play pivotal roles in the development of malignant tumors and serve as important targets for cancer diagnosis, treatment and prognosis. This review introduces the structural features, biological effects, and regulatory mechanisms of the RGS family, highlights the recent studies of specific roles of RGS proteins in multiple cancer types, and further explains the general characteristics of RGS in Pan-cancer. In addition, this review summarizes the unique role of RGS in tumor microenvironments as well as the current efforts made on cancer therapy via targeting RGS proteins.

Key words: regulators of G-protein signaling, cancer, treatment, tumor microenvironment