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.
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Citation: 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
AP1, Tead, invasion, transcriptional regulation
Liu, Xiangfan; Li, Huapeng; Rajurkar, Mihir S.; Li, Qi; Cotton, Jennifer L.; Ou, Jianhong; Zhu, Lihua J.; Goel, Hira L.; Mercurio, Arthur M.; Park, Joo-Seop; Davis, Roger J.; and Mao, Junhao, "Tead and AP1 Coordinate Transcription and Motility" (2016). Davis Lab Publications. 18.
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