Abstract 1685: Inactivation of a transcriptional variant of MAP1LC3A gene in human cancers.

Abstract

Abstract Autophagy functions to clear damaged or unfolded cellular components in the lysosomes as a survival pathway used by established cancers to sustain metabolism and tolerate stress. Autophagy, however, also suppress cancer initiation in liver and the accumulation of p62/SQSTM1 protein, a substrate for autophagic degradation, contributes to its tumorigenesis, suggesting that autophagy-related gene(s) may be actually inactivated in a part of human cancers at least. Recently, we have identified that a transcriptional variant of microtubule-associated protein 1 light chain 3A (LC3Av1), a member of human LC3 gene family, was frequently inactivated by aberrant DNA methylation in human cancers. Induction of wild-type LC3Av1 led to the decrease of p62 protein level, resulting in the inhibition of tumor growth, but not its mutant with the C-terminal glycine (lipidation site) changed to alanine. Thus, these results suggest that the impairment of autophagy through LC3Av1-silencing due to DNA methylation may be associated with tumorigenesis in various types of human cancer. Citation Format: Jun Inoue, Hua Bai, Tatsuyuki Kawano, Johji Inazawa. Inactivation of a transcriptional variant of MAP1LC3A gene in human cancers. [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 1685. doi:10.1158/1538-7445.AM2013-1685