Servizo de Oncología Médica, Complejo Hospitalario Universitario A Coruña (CHUAC), SERGAS, A Coruña, Spain.
Cell Mol Life Sci. 2013 Dec;70(23):4463-77. doi: 10.1007/s00018-013-1379-0. Epub 2013 May 29.
Epithelial-to-mesenchymal transition (EMT), one of the crucial steps for carcinoma cells to acquire invasive capacity, results from the disruption of cell-cell contacts and the acquisition of a motile mesenchymal phenotype. Although the transcriptional events controlling EMT have been extensively studied, in recent years, several posttranscriptional mechanisms have emerged as critical in the regulation of EMT during tumor progression. In this review, we highlight the regulation of posttranscriptional events in EMT by RNA-binding proteins (RBPs). RBPs are responsible for controlling pre-mRNA splicing, capping, and polyadenylation, as well as mRNA export, turnover, localization, and translation. We discuss the most relevant aspects of RBPs controlling the metabolism of EMT-related mRNAs, and describe the implication of novel posttranscriptional mechanisms regulating EMT in response to different signaling pathways. Novel insight into posttranscriptional regulation of EMT by RBPs is uncovering new therapeutic targets in cancer invasion and metastasis.
上皮-间充质转化(EMT)是癌细胞获得侵袭能力的关键步骤之一,它源于细胞-细胞接触的破坏和运动性间充质表型的获得。尽管控制 EMT 的转录事件已经得到了广泛的研究,但近年来,几种转录后机制已被证明在肿瘤进展过程中 EMT 的调控中至关重要。在这篇综述中,我们强调了 RNA 结合蛋白(RBPs)在 EMT 中的转录后事件调控。RBPs 负责控制前体 mRNA 的剪接、加帽和多聚腺苷酸化,以及 mRNA 的输出、周转、定位和翻译。我们讨论了控制 EMT 相关 mRNA 代谢的 RBPs 的最相关方面,并描述了调节 EMT 的新型转录后机制在响应不同信号通路时的意义。对 RBPs 调控 EMT 的转录后机制的新认识揭示了癌症侵袭和转移的新治疗靶点。