The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27Kip1
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Chunyan Wang1,2,3,*, Zhi Nie3,*, Zhongmei Zhou1, Hailin Zhang1, Rong Liu1, Jing Wu1,2,4, Junying Qin1,2, Yun Ma3, Liang Chen3, Shumo Li3, Wenlin Chen5, Fubing Li1,2, Peiguo Shi1,2, Yingying Wu3, Jian Shen3, Ceshi Chen1
1Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
2University of The Chinese Academy of Sciences, Beijing, China
3First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
4Department of Biochemistry, Kunming Medical University, Kunming, Yunnan, China
5Cancer Hospital, Kunming Medical University, Kunming, Yunnan, China
*These authors have contributed equally to this work
Ceshi Chen, e-mail: [email protected]
Keywords: TEAD4, KLF5, p27, hippo pathway, TNBC
Received: January 10, 2015 Accepted: April 10, 2015 Published: April 22, 2015
Growing evidence suggests that YAP/TAZ are mediators of the Hippo pathway and promote breast cancer. However, the roles of YAP/TAZ transcription factor partners TEADs in breast cancer remain unclear. Here we found that TEAD4 was expressed in breast cancer cell lines, especially in triple negative breast cancers (TNBC) cell lines. TEAD4 binds to KLF5. Knockdown of either TEAD4 or KLF5 in HCC1937 and HCC1806 cells induced the expression of CDK inhibitor p27. Depletion of either TEAD4 or KLF5 activated the p27 gene promoter and increased the p27 mRNA levels. Depletion of p27 partially prevents growth inhibition caused by TEAD4 and KLF5 knockdown. TEAD4 overexpression stimulated proliferation in vitro and tumor growth in mice, while stable knockdown of TEAD4 inhibited proliferation in vitro and tumor growth in mice. Thus TEAD4 and KLF5, in collaboration, promoted TNBC cell proliferation and tumor growth in part by inhibiting p27 gene transcription. TEAD4 is a potential target and biomarker for the development of novel therapeutics for breast cancer.
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