Tead and AP1 Coordinate Transcription and Motility

Cell Rep. 2016 Feb 9;14(5):1169-1180. doi: 10.1016/j.celrep.2015.12.104. Epub 2016 Jan 28.

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.

Keywords: AP1; Tead; invasion; transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement*
  • Cluster Analysis
  • DNA-Binding Proteins / metabolism*
  • Genome, Human
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Muscle Proteins / metabolism*
  • Neoplasm Invasiveness
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid / genetics
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • DNA-Binding Proteins
  • Muscle Proteins
  • TEAD4 protein, human
  • Transcription Factor AP-1
  • Transcription Factors
  • JNK Mitogen-Activated Protein Kinases