Abstract 1432: Role of ubiquitin-specific proteases 47 in epithelial-mesenchymal transition

Abstract

Abstract Metastatic spread from primary tumor is the last phase of cancer development. Approximately 90% of deaths from cancer are caused by metastasis. During the transition from a benign tumor to a metastatic one, tumor cells lose cell-cell contacts and gain cell motility for invasion. This is called epithelial-mesenchymal transition (EMT). EMT is considered to be a critical contributor of cancer metastasis. Hypoxia, which plays a critical role in development and tumor progression, orchestrates EMT through the coordinated regulation of different EMT regulators. In this study, we found that a series of ubiquitin specific proteases (USP), particularly USP47, were induced in human colon cancer cells (DLD-1, HT-29 and SW-480) under the hypoxic condition based on cDNA microarray data. USPs are a subfamily of deubiquitinating enzymes (DUB) that primarily belong to the cysteine protease family and are known to remove the monoubiquitin and polyubiquitin chains from specific target proteins. Knockdown of USP47 substantially decreased expression of mesenchymal markers. Furthermore, hypoxia-inducible factor (HIF), especially HIF-2α, was found to regulate transcription of USP47. These results suggest USP47 as a novel regulator of EMT under hypoxic conditions. Citation Format: Bae-Jung Choi, Young-Joon Surh. Role of ubiquitin-specific proteases 47 in epithelial-mesenchymal transition. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1432. doi:10.1158/1538-7445.AM2015-1432