缺氧诱导因子对肿瘤细胞上皮-间质转化的诱导机制

Mechanism of HIF induced epithelial mesenchymal transition

实体瘤组织内普遍存在低氧现象,缺氧诱导因子(hypoxia inducible factor,HIF)是缺氧条件下传递缺氧信号、介导缺氧效应的关键转录因子;上皮-间质转化(epithelial mesenchymal transitions,EMT)是一个多步骤有序可高度调节的过程,EMT的发生与多种蛋白分子、微环境及Micro RNA等有关,涉及多个信号转导通路和复杂的分子机制,在肿瘤细胞的侵袭和转移过程中扮演重要的角色。研究证实,低氧可通过转化生长因子-β(transforming growth factor-β,TGF-β)信号通路、Notch信号通路、Wnt信号通路、刺猬信号通路(hedgehog signaling pathway,Hedgehog)、肝细胞生长因子/肝细胞生长因子(HGF/Met)信号通路及多种转录因子等途径参与肿瘤EMT调控,目前通过抑制HIF来达到阻断EMT过程的研究日益增多且初见成效,揭示低氧诱导的EMT途径可能成为日后肿瘤治疗的新靶点,对于预防和治疗癌症具有重要意义。

Hypoxia is a common phenomenon in solid tumor, and hypoxia inducible factor（HIF） is a key transcription factor in the process of transmitting and mediating anoxic singals. Epithelial mesenchymal transitions（EMT） is a multi-step, ordered and highadjusted process, which palys an important role in tumor invasion and involves in various proteins, microenvironment, Micro RNA, signal pathway and molecular mechanism. Studies prove that hypoxia can regulate EMT through signal pathway of TGF-β, Notch, Wnt, Hedgehog and HGF/Met. Studies about blocking EMT through inhibition of HIF are effective, which indicates that HIFinduced EMT may be a new target of tumor therapy, and this means a lot to the prevention and therapy of cancer.