Izmir Biomedicine and Genome Center, 35340 Izmir, Turkey.
Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, 35340 Izmir, Turkey.
Cells. 2019 Aug 9;8(8):858. doi: 10.3390/cells8080858.
The epithelial to mesenchymal transition (EMT) and the mesenchymal to epithelial transition (MET) are two critical biological processes that are involved in both physiological events such as embryogenesis and development and also pathological events such as tumorigenesis. They present with dramatic changes in cellular morphology and gene expression exhibiting acute changes in E-cadherin expression. Despite the comprehensive understanding of EMT, the regulation of MET is far from being understood. To find novel regulators of MET, we hypothesized that such factors would correlate with expression. Bioinformatics examination of several expression profiles suggested as a strong candidate. Depletion of at the onset of MET severely impaired the progression to the epithelial state. This MET defect was explained, in part, by the absence of E-cadherin at the plasma membrane. Moreover, during MET, ELF3 interacts with the promoter and activates its expression. Our findings present novel insights into the regulation of MET and reveal ELF3 as an indispensable guardian of the epithelial state. A better understanding of MET will, eventually, lead to better management of metastatic cancers.
上皮间质转化(EMT)和间质上皮转化(MET)是两个关键的生物学过程,涉及胚胎发生和发育等生理事件以及肿瘤发生等病理事件。它们在细胞形态和基因表达上表现出显著的变化,表现为 E-钙黏蛋白表达的急剧变化。尽管对 EMT 有了全面的了解,但 MET 的调控还远未被理解。为了寻找 MET 的新调控因子,我们假设这些因子与表达相关。对几个表达谱的生物信息学分析表明是一个强有力的候选者。在 MET 开始时耗尽会严重损害向上皮状态的进展。这种 MET 缺陷部分是由于质膜上没有 E-钙黏蛋白。此外,在 MET 期间,ELF3 与 启动子相互作用并激活其表达。我们的发现为 MET 的调控提供了新的见解,并揭示了 ELF3 作为上皮状态不可或缺的守护者。对 MET 的更好理解最终将导致转移性癌症的更好管理。