Abstract 4142: Regulation of tumor suppressor decorin by APE1 in head and neck squamous cell carcinoma

Abstract

Abstract Oral cancers have a high rate of recurrence, and a tendency to develop treatment resistance. From 2009 to 2013, Kentucky had a disproportionately higher incidence of invasive oral cancers and resultant higher mortality compared to the national average (SEER & NPCR, Kentucky Cancer Registry). Apurinic/Apyrimidinic endonuclease (APE1) is a key protein in DNA repair, and an important transcriptional regulator. Gene array analysis in pMEFs expressing wild-type APE1 and extremely low levels of APE1 showed an eight-fold reduction of tumor suppressor decorin (DCN), with wild-type APE1. Decorin is a known tumor suppressor and extracellular matrix protein, which can suppress tumor proliferation, migration and angiogenesis. Tumors with decreased decorin are associated with increased mortality. These studies aim to elucidate APE1’s role in decorin regulation in oral cancer and identify biomarkers, which may aid in diagnosis, treatment, or predicting prognosis. Immunohistochemistry studies of head and neck squamous cell carcinoma from Kentuckians were analyzed aided by Aperio’s high resolution scanning capabilities, and software. Analysis showed a significant decrease in decorin in both tumor and carcinoma in situ compared to benign tissue. Whereas, APE1 was significantly increased in tumors. Additionally there was a significant negative correlation between APE1 and decorin total protein in carcinoma in situ. This data supports that increased APE1 may deplete decorin. Superoxide Dismutase 3, which is important in detoxifying extracellular ROS, was also significantly decreased in tumor and in carcinoma in situ. This along with previous research showing increased ROS in the tumor microenvironment and APE1 activation by ROS may explain the origination of decorin suppression. We hypothesize that the overexpression of APE1 in early stages of oral cancer leads to diminished decorin translation, which may drive cancer progression and increase mortality. Better understanding how APE1 influences tumor suppressors may eventually aid in development of therapeutics that would increase patient survival. Citation Format: Christina A. Wicker, Timothy L. Scott, Rangaswamy Suganya, Susan M. Arnold, Yolanda M. Brill, Craig M. Horbinski, Dana Napier, Joseph Valentino, Mahesh R. Kudrimoti, Guoqiang Yu, Tadahide Izumi. Regulation of tumor suppressor decorin by APE1 in head and neck squamous cell carcinoma [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 4142. doi:10.1158/1538-7445.AM2017-4142