Li Xiang, Lyu Yuan, Li Junqi, Wang Xinjun
Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Henan Joint International Laboratory of Glioma Metabolism and Microenvironment Research, Henan Provincial Department of Science and Technology, Zhengzhou, China.
Front Oncol. 2022 Sep 27;12:946086. doi: 10.3389/fonc.2022.946086. eCollection 2022.
The activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) is an intrinsically disordered protein that regulates the survival and death of cancer cells by modulating autophagy. Although the roles of autophagy in cancer are controversial and context-dependent, inhibition of autophagy under some circumstances can be a useful strategy for cancer therapy. As AMBRA1 is a pivotal autophagy-associated protein, targeting AMBRA1 similarly may be an underlying strategy for cancer therapy. Emerging evidence indicates that AMBRA1 can also inhibit cancer formation, maintenance, and progression by regulating c-MYC and cyclins, which are frequently deregulated in human cancer cells. Therefore, AMBRA1 is at the crossroad of autophagy, tumorigenesis, proliferation, and cell cycle. In this review, we focus on discussing the mechanisms of AMBRA1 in autophagy, mitophagy, and apoptosis, and particularly the roles of AMBRA1 in tumorigenesis and targeted therapy.
贝林1调节自噬蛋白1（AMBRA1）中的激活分子是一种内在无序蛋白，可通过调节自噬来调控癌细胞的存活和死亡。尽管自噬在癌症中的作用存在争议且依赖于具体情况，但在某些情况下抑制自噬可能是一种有用的癌症治疗策略。由于AMBRA1是一种关键的自噬相关蛋白，类似地靶向AMBRA1可能是癌症治疗的一种潜在策略。新出现的证据表明，AMBRA1还可通过调节c-MYC和细胞周期蛋白来抑制癌症的形成、维持和进展，而这些蛋白在人类癌细胞中经常失调。因此，AMBRA1处于自噬、肿瘤发生、增殖和细胞周期的交叉点。在本综述中，我们重点讨论AMBRA1在自噬、线粒体自噬和凋亡中的机制，特别是AMBRA1在肿瘤发生和靶向治疗中的作用。
