由GNA13和GNA12基因编码的Gα13和Gα12,分别,是Gα蛋白G12家族的成员,以及它们相关的Gβγ亚基,介导来自特定G蛋白偶联受体(GPCRs)的信号传导。晚期前列腺癌的GPCRs表达增加,如CXC基序趋化因子受体4(CXCR4),溶血磷脂酸受体(LPAR),和蛋白酶激活受体1(PAR-1)。这些GPCRs通过G12家族发出信号,或者专门通过Gα13,通常除了其他G蛋白。Gα13的作用可能与Gα12的作用不同,并且Gα13在前列腺癌的发生和发展中的作用在很大程度上尚未被研究。Gα13对前列腺癌细胞迁移和侵袭的致癌作用已被证实。但对线粒体功能和氧化应激等其他生物过程知之甚少。目前关于Gα13和氧化应激之间联系的知识是基于GPCR-Gα13信号传导降低超氧化物水平的动物研究,组成型活性Gα13的过表达促进了抗氧化基因的激活。在人体样本中,线粒体超氧化物歧化酶2(SOD2)与前列腺癌风险和预后Gleason分级相关。然而,SOD2在前列腺癌细胞中的过表达对基础和氧化应激条件下的细胞生长和存活产生了矛盾的结果。因此,有必要探讨Gα13在前列腺癌发生发展中的作用,以及在氧化应激条件下Gα13对前列腺癌细胞生长中SOD2的影响。
Gα13 and Gα12, encoded by the GNA13 and GNA12 genes, respectively, are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors (GPCRs). Advanced prostate cancers have increased expression of GPCRs such as CXC Motif Chemokine Receptor 4 (CXCR4), lysophosphatidic acid receptor (LPAR), and protease activated receptor 1 (PAR-1). These GPCRs signal through either the G12 family, or through Gα13 exclusively, often in addition to other G proteins. The effect of
Gα13 can be distinct from that of Gα12, and the role of
Gα13 in prostate cancer initiation and progression is largely unexplored. The oncogenic effect of
Gα13 on cell migration and invasion in prostate cancer has been characterized, but little is known about other biological processes such as mitochondrial function and oxidative stress. Current knowledge on the link between
Gα13 and oxidative stress is based on animal studies in which GPCR-
Gα13 signaling decreased superoxide levels, and the overexpression of constitutively active Gα13 promoted antioxidant gene activation. In human samples, mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason grade. However, overexpression of SOD2 in prostate cancer cells yielded conflicting results on cell growth and survival under basal versus oxidative stress conditions. Hence, it is necessary to explore the effect of Gα13 on prostate cancer tumorigenesis, as well as the effect of
Gα13 on SOD2 in prostate cancer cell growth under oxidative stress conditions.