Göttgens E-L, Span P N, Zegers M M
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Int Rev Cell Mol Biol. 2016;327:163-194. doi: 10.1016/bs.ircmb.2016.06.003. Epub 2016 Jul 30.
The transformation of polarized epithelial cells into cells with mesenchymal characteristics by the morphogenetic process of epithelial-mesenchymal transition (EMT) is a well-characterized process essential for embryonic development and associated with cancer progression. EMT is a program driven by changes in gene expression induced by several EMT-specific transcription factors, which inhibit the expression of cell-cell adhesion proteins and other epithelial markers, causing a characteristic loss of cell-cell adhesion, a switch to mesenchymal cell morphology, and increased migratory capabilities. Recently, it has become apparent that in addition to these transcriptionally regulated changes, EMT may also be regulated posttranscriptionally, that is, by alternative splicing. Specifically, the epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) have been described as epithelial-specific splicing master regulators specifically involved in EMT-associated alternative splicing. Here, we discuss the regulation of ESRP activity, as well as the evidence supporting a causal role of ESRPs in EMT.
通过上皮-间质转化（EMT）的形态发生过程，极化上皮细胞转变为具有间质特征的细胞，这是一个已被充分表征的过程，对胚胎发育至关重要且与癌症进展相关。EMT是一个由几种EMT特异性转录因子诱导的基因表达变化驱动的程序，这些转录因子抑制细胞间粘附蛋白和其他上皮标志物的表达，导致细胞间粘附的特征性丧失、转变为间质细胞形态以及迁移能力增强。最近，很明显除了这些转录调控的变化外，EMT也可能在转录后受到调控，即通过可变剪接。具体而言，上皮剪接调节蛋白1和2（ESRP1和ESRP2）已被描述为上皮特异性剪接主调节因子，特别参与与EMT相关的可变剪接。在这里，我们讨论ESRP活性的调节，以及支持ESRP在EMT中起因果作用的证据。
