title: The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27Kip1.
abstract: 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.
authors.affiliation: Key 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.|University of The Chinese Academy of Sciences, Beijing, China.|First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Nie
authors.affiliation: Key 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.
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Key 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.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key 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.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Key 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.|University of The Chinese Academy of Sciences, Beijing, China.|Department of Biochemistry, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key 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.|University of The Chinese Academy of Sciences, Beijing, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Qin
authors.affiliation: First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Shumo
authors.initials: S
authors.lastname: Li
authors.affiliation: Cancer Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key 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.|University of The Chinese Academy of Sciences, Beijing, China.
authors.forename: Fubing
authors.initials: F
authors.lastname: Li
authors.affiliation: Key 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.|University of The Chinese Academy of Sciences, Beijing, China.
authors.forename: Peiguo
authors.initials: P
authors.lastname: Shi
authors.affiliation: First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.affiliation: Key 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.
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009124:Muscle Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C436291:CDKN1B protein, human; D004268:DNA-Binding Proteins; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D009124:Muscle Proteins; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Hippo pathway; KLF5; TEAD4; TNBC; p27