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

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 br...

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Autores principales: Wang, Chunyan, Nie, Zhi, Zhou, Zhongmei, Zhang, Hailin, Liu, Rong, Wu, Jing, Qin, Junying, Ma, Yun, Chen, Liang, Li, Shumo, Chen, Wenlin, Li, Fubing, Shi, Peiguo, Wu, Yingying, Shen, Jian, Chen, Ceshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627338/
https://www.ncbi.nlm.nih.gov/pubmed/25970772
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author Wang, Chunyan
Nie, Zhi
Zhou, Zhongmei
Zhang, Hailin
Liu, Rong
Wu, Jing
Qin, Junying
Ma, Yun
Chen, Liang
Li, Shumo
Chen, Wenlin
Li, Fubing
Shi, Peiguo
Wu, Yingying
Shen, Jian
Chen, Ceshi
author_facet Wang, Chunyan
Nie, Zhi
Zhou, Zhongmei
Zhang, Hailin
Liu, Rong
Wu, Jing
Qin, Junying
Ma, Yun
Chen, Liang
Li, Shumo
Chen, Wenlin
Li, Fubing
Shi, Peiguo
Wu, Yingying
Shen, Jian
Chen, Ceshi
author_sort Wang, Chunyan
collection PubMed
description 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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spelling pubmed-46273382015-12-02 The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27(Kip1) Wang, Chunyan Nie, Zhi Zhou, Zhongmei Zhang, Hailin Liu, Rong Wu, Jing Qin, Junying Ma, Yun Chen, Liang Li, Shumo Chen, Wenlin Li, Fubing Shi, Peiguo Wu, Yingying Shen, Jian Chen, Ceshi Oncotarget Research Paper 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. Impact Journals LLC 2015-04-22 /pmc/articles/PMC4627338/ /pubmed/25970772 Text en Copyright: © 2015 Wang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wang, Chunyan
Nie, Zhi
Zhou, Zhongmei
Zhang, Hailin
Liu, Rong
Wu, Jing
Qin, Junying
Ma, Yun
Chen, Liang
Li, Shumo
Chen, Wenlin
Li, Fubing
Shi, Peiguo
Wu, Yingying
Shen, Jian
Chen, Ceshi
The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27(Kip1)
title The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27(Kip1)
title_full The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27(Kip1)
title_fullStr The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27(Kip1)
title_full_unstemmed The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27(Kip1)
title_short The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27(Kip1)
title_sort interplay between tead4 and klf5 promotes breast cancer partially through inhibiting the transcription of p27(kip1)
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627338/
https://www.ncbi.nlm.nih.gov/pubmed/25970772
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