Krüppel-like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF-ß1/Smad/snail pathway.

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-ß1 pathway, whereas enforced KLF4 overexpression activated TGF-ß1, phosphorylation of Smad 2/3 and Snail expression, and restored stemness and mesenchymal phenotypes. Furthermore, TGF-ß1 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-ß1/Smad/Snail pathway in Lgr5+ CD44+ EpCAM+ colorectal CSCs.