TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition.
The TAZ transcription co-activator has been shown to promote cell proliferation and to induce epithelial-mesenchymal transition. Recently we have demonstrated that TAZ is phosphorylated and inhibited by the Hippo tumor suppressor pathway, which is altered in human cancer. The mechanism of TAZ-mediated transcription is unclear. We demonstrate here that TEAD is a key downstream transcription factor mediating the function of TAZ. Disruption of TEAD-TAZ binding or silencing of TEAD expression blocked the function of TAZ to promote cell proliferation and to induce epithelial-mesenchymal transition, demonstrating TEAD as a key downstream effector of TAZ. We also identified CTGF, a gene that regulates cell adhesion, proliferation, and migration, as a direct target of TAZ and TEAD. Our study establishes a functional partnership between TAZ and TEAD under negative regulation by the Hippo signaling pathway.
Zhang
Heng
H
Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; School of Life Science Fudan University, Shanghai, China 200032.
Liu
Chen-Ying
CY
Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; School of Life Science Fudan University, Shanghai, China 200032.
Zha
Zheng-Yu
ZY
Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032.
Zhao
Bin
B
Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093-0815.
Yao
Jun
J
Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032.
Zhao
Shimin
S
Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; School of Life Science Fudan University, Shanghai, China 200032.
Xiong
Yue
Y
Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
Lei
Qun-Ying
QY
Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; Department of Biological Chemistry, School of Medicine, Fudan University, Shanghai, China 200032. Electronic address: qlei@fudan.edu.cn.
Guan
Kun-Liang
KL
Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093-0815; Department of Biological Chemistry, School of Medicine, Fudan University, Shanghai, China 200032. Electronic address: kuguan@ucsd.edu.