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The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27(Kip1)

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机构: [1]Chinese Acad Sci, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China [2]Univ Chinese Acad Sci, Beijing, Peoples R China [3]Kunming Med Univ, Affiliated Hosp 1, Kunming, Yunnan, Peoples R China [4]Kunming Med Univ, Dept Biochem, Kunming, Yunnan, Peoples R China [5]Kunming Med Univ, Canc Hosp, Kunming, Yunnan, Peoples R China
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关键词: TEAD4 KLF5 p27 hippo pathway TNBC

摘要:
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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出版当年[2016]版:
大类 | 1 区 医学
小类 | 2 区 细胞生物学 2 区 肿瘤学
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Q1 CELL BIOLOGY Q1 ONCOLOGY
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第一作者机构: [1]Chinese Acad Sci, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China [2]Univ Chinese Acad Sci, Beijing, Peoples R China [3]Kunming Med Univ, Affiliated Hosp 1, Kunming, Yunnan, Peoples R China
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通讯机构: [1]Chinese Acad Sci, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China
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