2. Academic Validation
  3. YAP promotes breast cancer metastasis by repressing growth differentiation factor-15

YAP promotes breast cancer metastasis by repressing growth differentiation factor-15

  • Biochim Biophys Acta Mol Basis Dis. 2018 May;1864(5 Pt A):1744-1753. doi: 10.1016/j.bbadis.2018.02.020.
Ting Wang 1,  Beibei Mao 2,  Chi Cheng 3,  Zhuangzhi Zou 4,  Junling Gao 1,  Yanglu Yang 5,  Tong Lei 1,  Xiaolong Qi 5,  Zengqiang Yuan 6,  Wentong Xu 7,  Zhongbing Lu 8
Affiliations

Affiliations

  • 1 College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 State key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 3 General Surgery Center, Chinese PLA General Hospital, Beijing 100853, China.
  • 4 State key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Huazhong University of Science & Technology, Wuhan 430074, China.
  • 5 College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; State key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 6 The Brain Science Center, Institute of Basic Medical Sciences, Beijing 100850, China; Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China. Electronic address: zyuan620@yahoo.com.
  • 7 General Surgery Center, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: xuwentong@medmail.com.cn.
  • 8 College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: luzhongbing@ucas.ac.cn.
PMID: 29499325 DOI: 10.1016/j.bbadis.2018.02.020
Abstract

The transcriptional co-activator Yes-associated protein (YAP) has been implicated as an oncogene and is found to promote breast Cancer metastasis. However, the pro-metastatic mechanism of YAP remains unclear. Here, we demonstrated that YAP functions as a transcriptional repressor of growth differentiation factor-15 (GDF15), a divergent member of the transforming growth factor superfamily, in several breast Cancer cell lines. Functionally, knockdown of YAP decreased, whereas knockdown of GDF15 increased, the metastatic potential of breast Cancer cells. More than that, the reduced metastasis in YAP-depleted cells could be reversed by simultaneous knockdown of GDF15. Mechanistically, the repressive effect of YAP on GDF15 requires its transcriptional factor TEAD (TEA domain family). In addition, YAP recruits polycomb repressive complex 2 (PRC2) to tri-methylate histone H3 lysine 27 in the promoter region of GDF15. Co-immunoprecipitation experiments demonstrated that YAP and enhancer of zeste 2 PRC2 subunit (EZH2) physically interact with each other. In conclusion, our data reveal that YAP promotes metastasis of breast Cancer cells by repressing GDF15 transcription and present a novel molecular mechanism underlying the pro-metastasis function of YAP oncoprotein, with the implication of a therapeutic avenue for breast Cancer treatment.

Keywords

Breast cancer metastasis; EZH2; GDF15; YAP.

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