Tead and AP1 Coordinate Transcription and Motility.
Tead and AP1 Coordinate Transcription and Motility.
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DOI：
10.1016/j.celrep.2015.12.104
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发表时间：
2016-02-09
期刊：
影响因子：
8.8
通讯作者：
Mao J
中科院分区：
文献类型：
--
作者：
Liu X;Li H;Rajurkar M;Li Q;Cotton JL;Ou J;Zhu LJ;Goel HL;Mercurio AM;Park JS;Davis RJ;Mao J
Tead家族转录因子是Hippo-Yap通路的主要细胞内介质。尽管Hippo信号在肿瘤发生中的重要性，但对癌细胞中Tead依赖性下游致癌程序和靶基因的了解仍然很少。在这里，我们的特点Tead 4介导的转录网络在不同范围的癌细胞，包括神经母细胞瘤，结直肠癌，肺癌和子宫内膜癌。通过对Tead 4、JunD和Fra 1/2的交叉全基因组染色质占有率分析，我们发现Tead 4与AP 1转录因子协同作用，协调靶基因的转录。我们发现，Tead-AP 1相互作用是JNK独立的，但参与SRC 1 -3共激活子，以促进下游转录。此外，我们表明Tead-AP 1合作调节Dock-Rac/CDC 42模块的活性，并驱动一组独特的核心靶基因的表达，从而指导细胞迁移和侵袭。总之，我们的数据揭示了一个关键的调控机制，潜在的Tead和AP 1控制的转录和功能输出在癌细胞中。
The Tead family transcription factors are the major intracellular mediators of the Hippo-Yap pathway. Despite the importance of Hippo signaling in tumorigenesis, Tead-dependent downstream oncogenic programs and target genes in cancer cells remain poorly understood. Here we characterize Tead4-mediated transcriptional networks in a diverse range of cancer cells, including neuroblastoma, colorectal, lung, and endometrial carcinomas. By intersecting genome-wide chromatin occupancy analyses of Tead4, JunD and Fra1/2, we find that Tead4 cooperates with AP1 transcription factors to coordinate target gene transcription. We find that Tead-AP1 interaction is JNK independent, but engages the SRC1-3 coactivators to promote downstream transcription. Furthermore we show that Tead-AP1 cooperation regulates the activity of the Dock-Rac/CDC42 module and drives the expression of a unique core set of target genes, thereby directing cell migration and invasion. Together, our data unveil a critical regulatory mechanism underlying Tead- and AP1-controlled transcriptional and functional outputs in cancer cells.