Implications of a Neuronal Receptor Family, Metabotropic Glutamate Receptors, in Cancer Development and Progression

Abstract

Cancer is the second leading cause of death, and incidences are increasing globally. Simply defined, cancer is the uncontrolled proliferation of a cell, and depending on the tissue of origin, the cancer etiology, biology, progression, prognosis, and treatment will differ. Carcinogenesis and its progression are associated with genetic factors that can either be inherited and/or acquired and are classified as an oncogene or tumor suppressor. Many of these genetic factors converge on common signaling pathway(s), such as the MAPK and PI3K/AKT pathways. In this review, we will focus on the metabotropic glutamate receptor (mGluR) family, an upstream protein that transmits extracellular signals into the cell and has been shown to regulate many aspects of tumor development and progression. We explore the involvement of members of this receptor family in various cancers that include breast cancer, colorectal cancer, glioma, kidney cancer, melanoma, oral cancer, osteosarcoma, pancreatic cancer, prostate cancer, and T-cell cancers. Intriguingly, depending on the member, mGluRs can either be classified as oncogenes or tumor suppressors, although in general most act as an oncogene. The extensive work done to elucidate the role of mGluRs in various cancers suggests that it might be a viable strategy to therapeutically target glutamatergic signaling.

Keywords

• cancer
• guanine nucleotide binding–protein coupled receptor
• metabotropic glutamate receptor
• glutamate
• phospholipase C
• adenylyl cyclase