TEAD mediates YAP-dependent gene induction and growth control (original) (raw)

  1. Bin Zhao1,2,
  2. Xin Ye3,
  3. Jindan Yu4,
  4. Li Li1,2,
  5. Weiquan Li5,
  6. Siming Li5,
  7. Jianjun Yu4,
  8. Jiandie D. Lin5,
  9. Cun-Yu Wang6,
  10. Arul M. Chinnaiyan4,
  11. Zhi-Chun Lai3, and
  12. Kun-Liang Guan1,7
  13. 1 Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA;
  14. 2 Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA;
  15. 3 Department of Biology and Intercollege Graduate Program in Genetics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA;
  16. 4 Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
  17. 5 Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA;
  18. 6 Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California at Los Angeles School of Dentistry, Los Angeles, California 90095, USA

Abstract

The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent gene expression. TEAD is also required for YAP-induced cell growth, oncogenic transformation, and epithelial–mesenchymal transition. CTGF is identified as a direct YAP target gene important for cell growth. Moreover, the functional relationship between YAP and TEAD is conserved in Drosophila Yki (the YAP homolog) and Scalloped (the TEAD homolog). Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP.

Footnotes