Abstract
Abstract Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) are RNA binding proteins which are recently known to be involved in tumor progression via regulation of alternative splicing of cancer-associated genes. However, their expression and clinical significance in ovarian cancer remain unclear. Here, we found that ESRP1 and ESRP2 gene expression is upregulated in ovarian cancer cells compared with immortalized ovarian surface epithelial (IOSE) cells and their overexpression at protein level was also confirmed in ovarian cancer tissues. Consistent with TCGA data of ESRP1 gene amplification, higher ESRP1 gene copy number was observed in ovarian cancer cells compared with IOSE cells, whereas there was little correlation between gene copy number and gene expression in ovarian cancer cells. Importantly, their gene expression was inversely correlated with DNA methylation in ovarian cancer cells and ESRP2 overexpression in ovarian cancer was significantly associated with DNA hypomethylation (P= 0.036). Of note, TCGA data analysis showed that high ESRP1 gene expression is significantly associated with shorter 5-year survival of patients with ovarian cancer. Ectopic expression of ESRP1 in ESRP1 low-expressing mesenchymal type ovarian cancer cells increased cell proliferation, whereas it suppresses cell migration. Furthermore, our results revealed that the effect of ESRP1 overexpression on cell proliferation and migration is related to activation of the Akt/CyclinD pathway and increased of E-cadherin expression. In conclusion, our findings suggest that ESRP1 overexpression is associated with poor outcome of patients and ESRP1 may play a cancer-promoting role in ovarian cancer. Citation Format: Mi Jeong Kwon. ESRP1 overexpression and its role in ovarian cancer [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 4357. doi:10.1158/1538-7445.AM2017-4357
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