کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2040531 | 1073116 | 2016 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Tead and AP1 Coordinate Transcription and Motility Tead and AP1 Coordinate Transcription and Motility](/preview/png/2040531.png)
• Tead and AP1 coordinate downstream transcription in diverse cancer cells
• JNK-independent Tead-AP1 interaction engages SRC1–3 co-activators
• Tead and AP1 regulate the activity of Dock-Rac/CDC42 module
• Tead-AP1 cooperation controls migration and invasion through a core set of target genes
SummaryThe 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 co-activators 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.
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Journal: - Volume 14, Issue 5, 9 February 2016, Pages 1169–1180