Abstract 284: Down-regulated Kruppel-like factor 4 induces the migration and epithelial-mesenchymal transition in human hepatoma cells.

Abstract

Abstract The transcriptional factor Kruppel-like factor 4 (KLF4) plays important roles in development, stemness, and tumorigenesis. Several studies have suggested that KLF4 is important in various tumors; however limited information is available on the detailed function of KLF4 in hepatocellular carcinoma. The objective of this study was to examine the functional roles of KLF4 in metastasis of hepatoma cells. In order to investigate the role of KLF4 in the progression of hepatocellular carcinoma, we used lentiviral transduction method to down-regulate KLF4 expression in Hep3B and HA22T/VGH hepatoma cell lines. The effects of KLF4 on cell migration, invasion and the expression of epithelial-mesenchymal transition (EMT) related proteins were evaluated in KLF4-knockdown hepatoma cells. Transwell migration assay and matrigel invasion assay revealed the migration and invasion abilities were significantly increased in KLF4-knockdown Hep3B or HA22T/VGH cells. Knockdown KLF4 in hepatoma cells resulted in decreased mRNA and protein expression of E-cadherin, and a concomitant increase of vimentin, MMP2 and MMP9. These results corresponded well with our finding that overexpression of KLF4 in Mahlavu hepatoma cells led to significant inhibition of cell migration and invasion through up-regulating E-cadherin and down-regulating vimentin, MMP2 and MMP9. Snail and Bmi1, repressors of E-cadherin gene expression, were also markedly decreased in KLF4-overexpressing Mahlavu cells. Therefore, these results together suggested that KLF4 is tightly involved in the epithelial-mesenchymal transition and metastasis in the tumor progression of hepatocellular carcinoma. Citation Format: Ming-Ta Sung, Hsin-Chen Lee, Cheng-Yuan Hsia, Chin-Wen Chi. Down-regulated Kruppel-like factor 4 induces the migration and epithelial-mesenchymal transition in human hepatoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 284. doi:10.1158/1538-7445.AM2013-284