UMMS Affiliation

Program in Molecular Medicine; Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network

Date

2-9-2016

Document Type

Article

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

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.

Rights and Permissions

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

Comments

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/

Related Resources

Link to Article in PubMed

Keywords

AP1, Tead, invasion, transcriptional regulation

PubMed ID

26832411

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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