上皮间质转化（EMT）是发育阶段上皮细胞转分化为间质细胞的过程之一，称为“完全EMT”。在上皮癌中，EMT，也称为“部分EMT”，与侵袭、转移和治疗耐药相关，并且由多种转录因子（通常称为EMT转录因子）引发。在这些调节EMT的转录因子中，ZEB1/2（ZEB1和ZEB2）、SNAIL和TWIST在驱动EMT过程（以下简称“EMT-TF”）中发挥着重要作用。其中，ZEB1/2与间充质标志蛋白的表达和各种癌症的侵袭性呈正相关。另一方面，TWIST和SNAIL也与癌的侵袭性相关，但与间充质标志蛋白表达相关性不高。有趣的是，除了肉瘤之外，在任何研究的侵袭性癌症病例中都没有同时检测到这些 EMT-TF。因此，只有一种或一些EMT-TF在侵袭性癌细胞中高水平表达。 EMT-TF 的表达受转化生长因子-β (TGF-β)（一种成熟的 EMT 诱导剂）与其他信号分子（例如活性 RAS 信号）的配合调节。本综述的重点是 EMT-TF 在侵袭性癌细胞中转录维持在足够高水平并在癌症进展过程中被 TGF-β 上调的分子机制。版权所有 © 2023。由 Elsevier Ltd 出版。

The epithelial-mesenchymal transition (EMT) is one of the processes by which epithelial cells transdifferentiate into mesenchymal cells in the developmental stage, known as "complete EMT." In epithelial cancer, EMT, also termed "partial EMT," is associated with invasion, metastasis, and resistance to therapy, and is elicited by several transcription factors, frequently referred to as EMT transcription factors. Among these transcription factors that regulate EMT, ZEB1/2 (ZEB1 and ZEB2), SNAIL, and TWIST play a prominent role in driving the EMT process (hereafter referred to as "EMT-TFs"). Among these, ZEB1/2 show positive correlation with both expression of mesenchymal marker proteins and the aggressiveness of various carcinomas. On the other hand, TWIST and SNAIL are also correlated with the aggressiveness of carcinomas, but are not highly correlated with mesenchymal marker protein expression. Interestingly, these EMT-TFs are not detected simultaneously in any studied cases of aggressive cancers, except for sarcoma. Thus, only one or some of the EMT-TFs are expressed at high levels in cells of aggressive carcinomas. Expression of EMT-TFs is regulated by transforming growth factor-β (TGF-β), a well-established inducer of EMT, in cooperation with other signaling molecules, such as active RAS signals. The focus of this review is the molecular mechanisms by which EMT-TFs are transcriptionally sustained at sufficiently high levels in cells of aggressive carcinomas and upregulated by TGF-β during cancer progression.Copyright © 2023. Published by Elsevier Ltd.