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

Oncotarget
Qingqing YanJide Wang

Abstract

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 v...Continue Reading

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Citations

Mar 18, 2020·Reproduction in Domestic Animals = Zuchthygiene·Limeng ZhangShujun Tian
May 22, 2017·Journal of Cancer Research and Clinical Oncology·Y R ParkSang Wook Kim
Dec 22, 2016·Biological Chemistry·Ellen Dickreuter, Nils Cordes
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Aug 22, 2020·Cancer Management and Research·Soyeon BangHongwei Zhang
Feb 6, 2019·Therapeutic Advances in Gastroenterology·Na Li, Ying Zhu

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Methods Mentioned

BETA
ChIP
immunoprecipitation
transfection
transfections
xenograft
reverse transcription PCR
PCR
ELISA

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