Gopal Krishnan Priya D, Golden Emily, Woodward Eleanor A, Pavlos Nathan J, Blancafort Pilar
Cancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia.
School of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway Perth, Perth 6009, Australia.
Cancers (Basel). 2020 Jan 21;12(2):259. doi: 10.3390/cancers12020259.
The Rab GTPase family of proteins are mediators of membrane trafficking, conferring identity to the cell membranes. Recently, Rab and Rab-associated factors have been recognized as major regulators of the intracellular positioning and activity of signaling pathways regulating cell growth, survival and programmed cell death or apoptosis. Membrane trafficking mediated by Rab proteins is controlled by intracellular localization of Rab proteins, Rab-membrane interactions and GTP-activation processes. Aberrant expression of Rab proteins has been reported in multiple cancers such as lung, brain and breast malignancies. Mutations in Rab-coding genes and/or post-translational modifications in their protein products disrupt the cellular vesicle trafficking network modulating tumorigenic potential, cellular migration and metastatic behavior. Conversely, Rabs also act as tumor suppressive factors inducing apoptosis and inhibiting angiogenesis. Deconstructing the signaling mechanisms modulated by Rab proteins during apoptosis could unveil underlying molecular mechanisms that may be exploited therapeutically to selectively target malignant cells.
Rab GTPase蛋白家族是膜运输的介质，赋予细胞膜特异性。最近，Rab及与Rab相关的因子已被公认为是调节细胞生长、存活及程序性细胞死亡或凋亡的信号通路在细胞内定位和活性的主要调节因子。由Rab蛋白介导的膜运输受Rab蛋白的细胞内定位、Rab-膜相互作用和GTP激活过程的控制。Rab蛋白的异常表达已在多种癌症中被报道，如肺癌、脑癌和乳腺癌。Rab编码基因的突变和/或其蛋白质产物的翻译后修饰会破坏细胞囊泡运输网络，调节致瘤潜力、细胞迁移和转移行为。相反，Rab也作为肿瘤抑制因子诱导细胞凋亡并抑制血管生成。解析Rab蛋白在细胞凋亡过程中调节的信号机制，可能揭示潜在的分子机制，这些机制可用于治疗，以选择性地靶向恶性细胞。
