Abstract 2131: The Arkadia-ESRP2 axis suppresses tumor progression: Analyses in clear cell renal cell carcinoma

<jats:title>Abstract</jats:title> <jats:p>Tumor-specific alternative splicing is implicated in the progression of cancer, including clear cell renal cell carcinoma (ccRCC), a major subtype of kidney cancer accounting for 70-80% of all kidney cancer patients. Using ccRCC RNA-sequencing data from The Cancer Genome Atlas, we found that epithelial splicing regulatory protein 2 (ESRP2), one of the key regulators of alternative splicing in epithelial cells, is expressed in ccRCC, while ESRP1 is decreased in most of the ccRCC as previously reported. ESRP2 mRNA expression did not correlate with the overall survival rate of ccRCC patients, but the expression of some ESRP-target exons, including ENAH exon 11a, ITGA6 exon 27, and SLK exon 13, correlated with the good prognosis and with the expression of Arkadia (also known as RNF111) in ccRCC. Arkadia, a RING-type E3 ligase, that is known to enhance TGF-β signaling activities, physically interacted with ESRP2, induced polyubiquitination, and modulated its splicing function. Arkadia and ESRP2 suppressed ccRCC tumor growth in a coordinated manner. Lower expression of Arkadia correlated with advanced tumor stages and poor outcomes in ccRCC patients. This study thus reveals a novel tumor-suppressive role of the Arkadia-ESRP2 axis in ccRCC.</jats:p> <jats:p>Citation Format: Anna Mizutani, Daizo Koinuma, Hiroyuki Seimiya, Kohei Miyazono. The Arkadia-ESRP2 axis suppresses tumor progression: Analyses in clear cell renal cell carcinoma. [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 2131. doi:10.1158/1538-7445.AM2015-2131</jats:p>