Eddy Kevinn, Chen Suzie
Graduate Program in Cellular and Molecular Pharmacology, School of Graduate Studies, Rutgers University, Piscataway, NJ 08854, USA.
Susan Lehman Cullman Laboratory for Cancer Research, Rutgers University, Piscataway, NJ 08854, USA.
Cancers (Basel). 2021 Jul 31;13(15):3874. doi: 10.3390/cancers13153874.
Like other cancers, melanomas are associated with the hyperactivation of two major cell signaling cascades, the MAPK and PI3K/AKT pathways. Both pathways are activated by numerous genes implicated in the development and progression of melanomas such as mutated , , and . Our lab was the first to identify yet another driver of melanoma, Metabotropic Glutamate Receptor 1 (protein: mGluR1, mouse gene: , human gene: ), upstream of the MAPK and PI3K/AKT pathways. Binding of glutamate, the natural ligand of mGluR1, activates MAPK and PI3K/AKT pathways and sets in motion the deregulated cellular responses in cell growth, cell survival, and cell metastasis. In this review, we will assess the proposed modes of action that mediate the oncogenic properties of mGluR1 in melanoma and possible application of anti-glutamatergic signaling modulator(s) as therapeutic strategy for the treatment of melanomas.
与其他癌症一样，黑色素瘤与两种主要细胞信号级联反应的过度激活有关，即丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）信号通路。这两条信号通路均由众多与黑色素瘤发生发展相关的基因激活，如 、 、 基因的突变体。我们实验室首次鉴定出黑色素瘤的另一个驱动因子——代谢型谷氨酸受体1（蛋白：mGluR1，小鼠基因： ，人类基因： ），它位于MAPK和PI3K/AKT信号通路的上游。mGluR1的天然配体谷氨酸结合后，激活MAPK和PI3K/AKT信号通路，并引发细胞生长、细胞存活和细胞转移中失控的细胞反应。在本综述中，我们将评估介导mGluR1在黑色素瘤中致癌特性的作用模式，以及抗谷氨酸能信号调节剂作为黑色素瘤治疗策略的可能应用。
