Abstract 3479: Targeting FoxM1 selectively depletes hepatic cancer stem cells

Abstract

Abstract Over-expression of the Forkhead box M1 (FoxM1) transcription factor coincides with highly aggressive, poorly differentiated hepatocellular carcinoma (HCC). Over-expression of FoxM1 in HCC also correlates with poorer overall survival after hepatectomy. Since HCC progression involves hepatic cancer stem cells (HCSCs), we considered the roles of FoxM1 in HCSCs. We found that FoxM1 expression correlates with the expression of the stemness genes in human HCC cell lines. Interestingly, depletion of FoxM1 in human HCC lines causes a selective reduction in the population of the CD90+ HCSCs due to selective apoptosis. Moreover, FoxM1 silencing decreases sphere formation potential of the same cell lines, suggesting that FoxM1 is critical for survival of the HCSCs. Consistent with the loss of HCSCs, depletion of FoxM1 causes decrease in tumorigenic potential of the HCC cells in vitro as well as inhibition of tumor formation in mouse xenografts. Furthermore, we found that FoxM1 directly regulates expression of CD44, previously shown to be important for the tumorigenic potential of CD90+ HCC cells. These studies have exciting implications in further considerations of FoxM1 as a target of HCC therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3479. doi:1538-7445.AM2012-3479