Program in Molecular Medicine; Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
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 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.
AP1, Tead, invasion, transcriptional regulation
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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/
DOI of Published Version
Cell Rep. 2016 Feb 9;14(5):1169-80. doi: 10.1016/j.celrep.2015.12.104. Epub 2016 Jan 28. Link to article on publisher's site
Liu X, Li H, Rajurkar MS, Li Q, Cotton JL, Ou J, Zhu LJ, Goel HL, Mercurio AM, Park J, Davis RJ, Mao J. (2016). Tead and AP1 Coordinate Transcription and Motility. Davis Lab Publications. https://doi.org/10.1016/j.celrep.2015.12.104. Retrieved from https://escholarship.umassmed.edu/davis/18
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.