Tzeng Hong-Tai, Wang Yi-Ching
Department of Pharmacology, National Cheng Kung University, College of Medicine, No.1, University Road, Tainan, 70101, Taiwan, People's Republic of China.
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, Taiwan, People's Republic of China.
J Biomed Sci. 2016 Oct 6;23(1):70. doi: 10.1186/s12929-016-0287-7.
A large group of small Rab GTPases which mediate secretory and endosomal membrane transport, as well as autophagosome biogenesis, are essential components of vesicle trafficking machinery. Specific Rab protein together with the cognate effectors coordinates the dynamics of trafficking pathway and determines the cargo proteins destination. Functional impairments of Rab proteins by mutations or post-translational modifications disrupting the regulatory network of vesicle trafficking have been implicated in tumorigenesis. Therefore, the vesicle transport regulators play essential roles in the mediation of cancer cell biology, including uncontrolled cell growth, invasion and metastasis. The context-dependent role of the same Rab to act as either an oncoprotein or tumor suppressor in different cancers is found. Such discrepancies may be due in part to the interaction of specific Rab protein with different effectors or cargos in various tumors. Here, we review recent advances in the roles of Rab GTPases in communicating with other effectors in tumor progression. In this review, we also emphasize dysregulation of Rab-mediated membrane delivery shifting normal cell behaviors toward malignancy. Thus, recovery of the dysregulated vesicle trafficking systems in cancer cells may provide future directions for potential strategy to restrain tumor progression.
一大类介导分泌和内体膜运输以及自噬体生物发生的小Rab GTP酶是囊泡运输机制的重要组成部分。特定的Rab蛋白与同源效应器共同协调运输途径的动态变化，并决定货物蛋白的目的地。Rab蛋白因突变或翻译后修饰而导致功能受损，破坏了囊泡运输的调控网络，这与肿瘤发生有关。因此，囊泡运输调节因子在介导癌细胞生物学过程中起着重要作用，包括不受控制的细胞生长、侵袭和转移。人们发现，同一Rab在不同癌症中作为癌蛋白或肿瘤抑制因子的作用取决于具体情况。这种差异可能部分归因于特定Rab蛋白在各种肿瘤中与不同效应器或货物的相互作用。在这里，我们综述了Rab GTP酶在肿瘤进展中与其他效应器相互作用方面的最新进展。在这篇综述中，我们还强调了Rab介导的膜递送失调使正常细胞行为向恶性转变。因此，恢复癌细胞中失调的囊泡运输系统可能为抑制肿瘤进展的潜在策略提供未来方向。
