Abstract 5742: Up-regulation of mitochondrial chaperone TRAP1 in cancer precursors associated with chronic inflammation

Abstract

Abstract Chronic ulcerative colitis (UC) is an inflammatory bowel disease that predisposes to colorectal cancer. In chronic UC patients, the colon epithelium undergoes repeated cycles of inflammation and tissue repair, resulting in oxidative stress and accumulation of reactive oxidative species (ROS). Excessive ROS can cause oxidative stress, which may subsequently lead to damage in DNA, proteins and lipids. Using proteomics analysis of colonic mucosa from UC patients with neoplasia, we identified TNF receptor-associated protein 1(TRAP1) in the UC cancer precursors. TRAP1 is a mitochondrial chaperone which protects against oxidative stress and apoptosis. We further investigated TRAP1 in the progression of UC-associated colorectal cancer using immunohistochemistry and tissue microarray. Quantification of protein oxidation in the colonic epithelia revealed that oxidative stress was present in the colonic mucosa in both UC patients with dysplasia/cancer (progressors) and UC patients without dysplasia/cancer (non-progressors). However, TRAP1 was only up-regulated in UC progressors, but not in the non-progressors. Moreover, up-regulation of TRAP1 preceded the histological changes: it was present in both the dysplastic and non-dysplastic tissue of the UC progressors. We then investigated the cellular proteome changes underlying oxidative stress, and found that up-regulation of TRAP1 could be induced by oxidative stress. These results suggest that UC cancer arises in the setting of oxidative stress. Such oxidative stress subsequently induces the cytoprotective protein TRAP1. TRAP1 in turn appears to promote cancer progression by preventing the oxidative-damaged epithelial cells from undergoing apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5742. doi:1538-7445.AM2012-5742