Abstract 855: Ube2v1 promotes epithelial mesenchymal transition and metastasis in colorectal cancer by epigenetically transcriptional suppression of autophagy

Abstract

Abstract Ubiquitination is one of the basic post-translational modifications for cellular homeostasis. The conjugating enzyme (E2) family plays as a bridge linking the first step mediated by E1 with the final step mediated by E3 in the ubiquitin-proteasomesystem. However, the role of Ube2v1, one of Ubiquitin-conjugating E2 enzyme variant proteins (Ube2v), in colorectal cancer (CRC) and autophagy is unclear. Here, we found that Ube2v1 is elevated in tumor samples of CRC patients and correlated with poorer survival of CRC patients. Furthermore, Ube2v1 promotes migration and invasion of CRC cells in vitro and boosts tumor growth and metastasis of CRC cells in vivo. Interestingly, Ube2v1 suppresses autophagy program and promotes EMT and metastasis of CRC cells in an autophagy dependent pattern in vitro and in vivo. Moreover, Rapamycin attenuates the enhanced in vitro migration and invasion and in vivo lung metastasis of Ube2v1 overexpression by inducing the autophagy pathway. Mechanistically, Ube2v1 increases histone H4 lysine 16 acetylation by down-regulating expression of Sirt1 and epigenetically suppresses gene expression of autophagy genes in colorectal cancer. In conclusion, Ube2v1 functions as a globalregulator for autophagy by epigenetically transcriptional suppression of autophagy, and consequently promotes EMT and metastasis of CRC. Our study functionally links Ube2v1, one member of E2 family in the ubiquitin-proteasome system toautophagy program in CRC progression and metastasis. Note: This abstract was not presented at the meeting. Citation Format: Tong Shen, Dong Ling Cai, Hong Yu Liu, Juan Wen Gan, Ming Li, Ru Jing Wang, Da Peng Guo, Qun Zhou, Xing Xing Lu, Shi Li, Na Li Sun, Ming Jian Li. Ube2v1 promotes epithelial mesenchymal transition and metastasis in colorectal cancer by epigenetically transcriptional suppression of autophagy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 855. doi:10.1158/1538-7445.AM2017-855