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KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2

The transcription factor Krüppel-like factor (KLF)8 plays an important role in the formation of several human tumors, including colorectal cancer. We recently identified four-and-a-half LIM protein 2 (FHL2) as a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However...

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Autores principales: Yan, Qingqing, Zhang, Wenjing, Wu, Yao, Wu, Meiyan, Zhang, Mengnan, Shi, Xinpeng, Zhao, Jinjun, Nan, Qingzhen, Chen, Ye, Wang, Long, Cheng, Tianming, Li, Jiachu, Bai, Yang, Liu, Side, Wang, Jide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694840/
https://www.ncbi.nlm.nih.gov/pubmed/26320172
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author Yan, Qingqing
Zhang, Wenjing
Wu, Yao
Wu, Meiyan
Zhang, Mengnan
Shi, Xinpeng
Zhao, Jinjun
Nan, Qingzhen
Chen, Ye
Wang, Long
Cheng, Tianming
Li, Jiachu
Bai, Yang
Liu, Side
Wang, Jide
author_facet Yan, Qingqing
Zhang, Wenjing
Wu, Yao
Wu, Meiyan
Zhang, Mengnan
Shi, Xinpeng
Zhao, Jinjun
Nan, Qingzhen
Chen, Ye
Wang, Long
Cheng, Tianming
Li, Jiachu
Bai, Yang
Liu, Side
Wang, Jide
author_sort Yan, Qingqing
collection PubMed
description The transcription factor Krüppel-like factor (KLF)8 plays an important role in the formation of several human tumors, including colorectal cancer. We recently identified four-and-a-half LIM protein 2 (FHL2) as a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which KLF8 affects FHL2-mediated tumor proliferation, EMT and metastasis remains unknown. Here, we showed that KLF8 overexpression promoted EMT and metastatic phenotypes. KLF8 expression was stimulated by transforming growth factor (TGF)-β1. Moreover, KLF8 acted as a potential EMT inducer by stimulating vimentin expression and inducing a loss of E-cadherin in stable KLF8-transfected cells. KLF8 overexpression induced a strong increase in FHL2 expression, and a positive correlation between the expression patterns of KLF8 and FHL2 was observed in CRC cells. Promoter reporter and chromatin immunoprecipitation (ChIP) assays demonstrated that KLF8 directly bound to and activated the human FHL2 gene promoter. However, siRNA-mediated repression of FHL2 in KLF8-overexpressing cells reversed the EMT and the proliferative and metastatic phenotypes. In vivo, KLF8 promoted FHL2-mediated proliferation and metastasis via orthotopic implantation. Taken together, this work identified KLF8-induced FHL2 activation as a novel and critical signaling mechanism underlying human breast/colorectal cancer invasion and metastasis.
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spelling pubmed-46948402016-01-20 KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2 Yan, Qingqing Zhang, Wenjing Wu, Yao Wu, Meiyan Zhang, Mengnan Shi, Xinpeng Zhao, Jinjun Nan, Qingzhen Chen, Ye Wang, Long Cheng, Tianming Li, Jiachu Bai, Yang Liu, Side Wang, Jide Oncotarget Research Paper The transcription factor Krüppel-like factor (KLF)8 plays an important role in the formation of several human tumors, including colorectal cancer. We recently identified four-and-a-half LIM protein 2 (FHL2) as a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which KLF8 affects FHL2-mediated tumor proliferation, EMT and metastasis remains unknown. Here, we showed that KLF8 overexpression promoted EMT and metastatic phenotypes. KLF8 expression was stimulated by transforming growth factor (TGF)-β1. Moreover, KLF8 acted as a potential EMT inducer by stimulating vimentin expression and inducing a loss of E-cadherin in stable KLF8-transfected cells. KLF8 overexpression induced a strong increase in FHL2 expression, and a positive correlation between the expression patterns of KLF8 and FHL2 was observed in CRC cells. Promoter reporter and chromatin immunoprecipitation (ChIP) assays demonstrated that KLF8 directly bound to and activated the human FHL2 gene promoter. However, siRNA-mediated repression of FHL2 in KLF8-overexpressing cells reversed the EMT and the proliferative and metastatic phenotypes. In vivo, KLF8 promoted FHL2-mediated proliferation and metastasis via orthotopic implantation. Taken together, this work identified KLF8-induced FHL2 activation as a novel and critical signaling mechanism underlying human breast/colorectal cancer invasion and metastasis. Impact Journals LLC 2015-07-15 /pmc/articles/PMC4694840/ /pubmed/26320172 Text en Copyright: © 2015 Yan 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
Yan, Qingqing
Zhang, Wenjing
Wu, Yao
Wu, Meiyan
Zhang, Mengnan
Shi, Xinpeng
Zhao, Jinjun
Nan, Qingzhen
Chen, Ye
Wang, Long
Cheng, Tianming
Li, Jiachu
Bai, Yang
Liu, Side
Wang, Jide
KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2
title KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2
title_full KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2
title_fullStr KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2
title_full_unstemmed KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2
title_short KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2
title_sort klf8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of fhl2
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694840/
https://www.ncbi.nlm.nih.gov/pubmed/26320172
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