ZEB家族调节上皮-间质转化的作用机制

The Mechanism of Regulation of EMT by ZEB Family

上皮-间质转化(epithelial-mesenchymal transition,EMT)是具有极性、相互粘连的上皮细胞转换为具有活动能力、能够在细胞基质间自由移动的间质细胞的过程,EMT在正常胚胎发育和肿瘤细胞的侵袭和转移过程中都扮演着重要的角色。最近的研究结果发现,E盒结合锌指蛋白(zinc fingerE-box-bindingprotein,ZEB)家族是EMT的诱导因素之一。ZEB在转录水平直接或者间接地抑制了E-钙粘着蛋白等粘附蛋白和一系列极性蛋白的表达,促进了上皮细胞向间质细胞的转换;同时ZEB不仅受到TGFβ、Snail、NF-κB、缺氧(hypoxia)等众多信号的调节,niR-200等小RNA也能在转录后调节ZEB的表达,可逆性调控EMT。

Epithelial-mesenchymal transition （EMT） is a process in which epithelial cells lose polarity and cell-cell contacts and turn in to a mesenchymal state characterized by increased cell mobility. EMT plays an important role in both embryogenesis and tumor invasion and migration. Recent researches have revealed that the zinc finger E-box-blnding protein （ZEB） family can induce EMT. ZEB 1/ZEB2 directly or indirectly represses the transcription of epithelial cell-cell junction and polarity genes by binding to E-box sequence, thus promoting the transition to mesonchymal cells. On the other hand, ZEB family members are not only regulated by signals such as TGFβ, Snail, NF-κB, hypoxia, but also targeted by miR-200 family in a reciprocal way.