Abstract 3754: Methionine adenosyltransferase IIα regulates histone methyltransferase G9a expression in colorectal cancer stem cells.

Abstract

Abstract Histone modification is critical for regulation of chromatin structure and gene transcription in cells and recent evidences have characterized that histone methylation may contribute to tumorigenesis and cancer malignancies. In general, the methyl donor for methylation is synthesized from S-adenosylmethionine (SAM), in a reaction catalyzed from methionine by methionine adenosyltransferase (MAT). Our previous studies have demonstrated the expression of histone methyltransferase G9a, which is responsible for histone H3 lysine 9 methylation, not only correlates to tumor aggressiveness but also plays a crucial role in regulation of colorectal cancer stem cells (CSCs), which endow high tumorigenecity, drive metastasis and therapy-resistance. We discover that G9a is enriched in CSCs and knockdown of its expression will promote differentiation, inhibit drug-resistance and metastatic ability of CSCs. Here, we further report that MATIIα expression is specifically elevated in the nucleus and interacts with G9a in CSCs. Overexpression of MATIIα in non-CSCs will increase G9a expression, self-renewal ability and stemness marker expression. In contrast, knockdown of MATIIα decreases G9a expression, it reveals that the self-renewal ability will be blocked in CSCs. Furthermore, inhibition of MATIIα expression by its inhibitor, SAM, can also decrease G9a expression and stem-cell like characteristics. Taken together, we first demonstrate that the expression and the function of G9a are both maintained by MATIIα in colorectal CSCs. These findings provide a new insight into understanding of the link between the metabolic enzyme and epigenetic regulator in CSCs, which may be a therapeutic target in the future. Citation Format: Kai-Chun Li, Shih-Ting Cha, Chia-Yu Chu, Min-Liang Kuo. Methionine adenosyltransferase IIα regulates histone methyltransferase G9a expression in colorectal cancer stem 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 3754. doi:10.1158/1538-7445.AM2013-3754