Abstract A48: Ube2v1 promotes EMT and metastasis by 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-proteasome system. 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 downregulating expression of Sirt1 and epigenetically suppresses gene expression of autophagy genes in colorectal cancer. In conclusion, Ube2v1 functions as a global regulator 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 to autophagy program in CRC progression and metastasis. Citation Format: Tong Shen, Lingdong Cai, Yuhong Liu, Jianming Li. Ube2v1 promotes EMT and metastasis by suppression of autophagy [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A48.