Figure 3.

Main signaling pathways involved in the regulation of cancer by metabotropic glutamate receptor (mGluR) and inotropic glutamate receptor (iGluR). Group I mGluRs are coupled to phospholipase C (PLC) while groups II and III are coupled to adenylate cyclase (AC). NMDAR are ligand-gated ion channels that mediate a rapid depolarization of the membrane. The binding of glutamate to the glutamate binding site acts as a first messenger and induces the depolarization of the membrane leading to the influx of Ca²⁺ in the intracellular space, followed by the activation of the corresponding signaling pathways. Glutamate is the agonist of AMPAR, and the channel opens when two sites are occupied by glutamate. Within the receptor, the GluN2 subunit plays a critical role in the determination of the Ca²⁺ permeability of the AMPAR. Upon binding of the amino-acid glutamate to its receptors, the intracellular signal transduction mechanisms induce the activation of different signaling pathways leading to cell proliferation and tumor growth.