A pivotal role of Krüppel-like factor 5 in regulation of cancer stem-like cells in hepatocellular carcinoma

In hepatocellular carcinoma (HCC), there exists a highly tumorigenic subset of cells defined by high expression of CD44 and CD133 that has been reported to contain cancer stem-like cells (CSCs). Kruppel-like factor 5 (KLF5) regulates many factors involved in cell cycle, migration, inflammation, angiogenesis and stemness and has cancer-promoting effects in some cancers. While some reports have indicated that KLF5 may have important roles in regulation of CSCs, what role, if any, KLF5 plays in regulation of CSCs in HCC remains to be elucidated. Flow cytometric analysis of CD44 and CD133 in HCC cell lines revealed subpopulations of CD44High/CD133High and CD44Low/CD133Low cells. We subsequently sorted these subpopulations and identified KLF5 as a gene that is significantly upregulated in CD44High/CD44High cells via RNA sequencing using next generation sequencing technology. Moreover, KLF5 overexpression enriched the CD44High/CD133High subpopulation and, consistent with the up-regulation of CD44High/CD133High ...