Complex changes in alternative pre-mRNA splicing play a central role in the epithelial-to-mesenchymal transition (EMT).
Complex changes in alternative pre-mRNA splicing play a central role in the epithelial-to-mesenchymal transition (EMT).
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DOI：
10.1016/j.semcancer.2012.04.003
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发表时间：
2012-10
影响因子：
14.5
通讯作者：
Carstens RP
中科院分区：
文献类型：
--
作者：
Warzecha CC;Carstens RP
上皮向间充质转化（EMT）是一个重要的发育过程，也涉及疾病病理生理，如癌症的进展和转移。近年来，大量的文献已经确定了重要的转录调节因子和基因表达程序的大规模变化，这些变化驱动了EMT期间发生的表型变化。然而，在过去的几年中，选择性剪接的广泛变化也在塑造EMT特征的细胞行为变化中发挥了深刻的作用。虽然FGFR2和p120-catenin中已知的剪接开关提示了更大的emt相关的选择性剪接程序，但最近对上皮剪接调节蛋白1和2 （ESRP1和ESRP2）的鉴定开始揭示这种全基因组的转录后网络。现在有几项研究已经证明了这种替代剪接程序的真正广泛范围。与EMT相关的剪接全局开关增加了一个重要的转录后控制层，该层与转录和表观遗传调节协调工作，影响细胞形状、极性和行为的复杂变化，介导上皮细胞和间充质细胞状态之间的转变。未来的挑战包括需要在个体基因和系统水平上研究这些剪接开关的功能后果。
The epithelial to mesenchymal transition (EMT) is an important developmental process that is also implicated in disease pathophysiology, such as cancer progression and metastasis. A wealth of literature in recent years has identified important transcriptional regulators and large-scale changes in gene expression programs that drive the phenotypic changes that occur during the EMT. However, in the past couple of years it has become apparent that extensive changes in alternative splicing also play a profound role in shaping the changes in cell behavior that characterize the EMT. While long known splicing switches in FGFR2 and p120-catenin provided hints of a larger program of EMT-associated alternative splicing, the recent identification of the epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) began to reveal this genome-wide post-transcriptional network. Several studies have now demonstrated the truly vast extent of this alternative splicing program. The global switches in splicing associated with the EMT add an important additional layer of post-transcriptional control that works in harmony with transcriptional and epigenetic regulation to effect complex changes in cell shape, polarity, and behavior that mediate transitions between epithelial and mesenchymal cell states. Future challenges include the need to investigate the functional consequences of these splicing switches at both the individual gene as well as systems level.
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DOI：
10.1083/jcb.131.6.1623
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bennett KL;Modrell B;Greenfield B;Bartolazzi A;Stamenkovic I;Peach R;Jackson DG;Spring F;Aruffo A
通讯作者：
Aruffo A
影响因子：
4.6
作者：
Gates, Julie;Mahaffey, James P.;Peifer, Mark
通讯作者：
Peifer, Mark
影响因子：
3.7
作者：
Gosens, Ilse;Sessa, Alessandro;Roepman, Ronald
通讯作者：
Roepman, Ronald
影响因子：
15.9
作者：
Brown, Rhonda L.;Reinke, Lauren M.;Cheng, Chonghui
通讯作者：
Cheng, Chonghui
影响因子：
64.5
作者：
Bear, JE;Svitkina, TM;Gertler, FB
通讯作者：
Gertler, FB