Open AccessKrüppel‐like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF‐β1/Smad/snail pathway
Author(s) -
Leng Zhengwei,
Li Yong,
Zhou Guojun,
Lv Xiaojiang,
Ai Walden,
Li Jianshui,
Hou Lingmi
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14882
Subject(s) - klf4 , cd44 , mesenchymal stem cell , smad , cancer research , cancer stem cell , epithelial–mesenchymal transition , microbiology and biotechnology , biology , lgr5 , stem cell , transforming growth factor , metastasis , sox2 , cancer , transcription factor , cell , biochemistry , genetics , gene
Krüppel‐like factor 4 (KLF4) was closely associated with epithelial‐mesenchymal transition and stemness in colorectal cancer stem cells (CSCs)‐enriched spheroid cells. Nonetheless, the underlying molecular mechanism is unclear. This study showed that KLF4 overexpression was accompanied with stemness and mesenchymal features in Lgr5 + CD44 + EpCAM + colorectal CSCs. KLF4 knockdown suppressed stemness, mesenchymal features and activation of the TGF‐β1 pathway, whereas enforced KLF4 overexpression activated TGF‐β1, phosphorylation of Smad 2/3 and Snail expression, and restored stemness and mesenchymal phenotypes. Furthermore, TGF‐β1 pathway inhibition invalidated KLF4‐facilitated stemness and mesenchymal features without affecting KLF4 expression. The data from the current study are the first to demonstrate that KLF4 maintains stemness and mesenchymal properties through the TGF‐β1/Smad/Snail pathway in Lgr5 + CD44 + EpCAM + colorectal CSCs.