Roles and Regulation of Epithelial Splicing Regulatory Proteins 1 and 2 in Epithelial-Mesenchymal Transition.
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.
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
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Göttgens
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
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Span
Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: mirjam.zegers@radboudumc.nl.
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Zegers
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D016601:RNA-Binding Proteins / Q000378:metabolism*
D016601:RNA-Binding Proteins
ESRP1; ESRP2; alternative splicing; carcinogenesis; cell signaling; epithelial–mesenchymal transition