mTORC2功能及其在血液肿瘤中作用的研究进展

Function of mTORC2 and Its Roles in Hematological Malignancies——Review

哺乳动物雷帕霉素靶蛋白复合体(mammalian target of rapamycin complex,mTORC)是细胞生长、存活、代谢的重要调控中心,它对维持生命有机体的正常生理活动和内稳态的平衡有着重要作用。mTORC根据其蛋白组份可分为mTORC1和mTORC2。mTORC2的主要组成蛋白有mTOR、Rictor、mLST8、Deptor、mSin1、Protor和Hsp70。mTORC2通过作用于Akt,PKCα和SGK1等来调控多项生命活动,如胚胎发育,细胞骨架重建,细胞迁移,蛋白质翻译和修饰等。mTOR信号通路异常已被证实与肿瘤相关,同时发现多种肿瘤发生与mTORC2及其异常调节信号通路相关。因此,对mTORC2组成、功能以及参与的信号通路的研究,可能为进一步研制其相关的靶向抑制药物乃至肿瘤治疗提供新思路。本综述将介绍mTORC2的组成结构、功能、参与的信号通路,及其在血液肿瘤中作用的研究进展。

Mammalian target of rapamycin complex（mTORC） is an important center for regulaling cellular growth,survival and metabolism.mTORC plays a vital role in maintenance of normal physiological activities and homeostasis in organism.According to protein components,mTORC can be divided into two distinct protein complexes： mTORC1 and mTORC2.The main protein components of mTORC2 include mTOR,Rictor,mLST8,Deptor,mSin1,Protor and Hsp70.By means of activating AKT,PKCα,SGK1 and so on,the mTORC regulates many vital activities：embryonic development,cytoskeleal reconstitution,cell migration and protein post-translational modification.The abnormality of mTORC2 signalting pathway has been confirmed to be associated with tumorigenesis,therefore,further understanding the components,functions and signalling pathway of mTORC2 will provide a new insights in developing targeted cancer therapy.In this review,the structure and signalling pathway of mTORC2 and its roles in hematological malignancies are discussed and summarised.