Abstract 1126: Tristetraprolin inhibits Twist1-induced cancer cell migration

Abstract

Abstract Epithelial-Mesenchymal Transition (EMT) enhances tumor cell migration. However, detail mechanisms for the regulation of EMT are not well known. Tristetraprolin (TTP) is an AU-rich element (ARE) binding protein that can promote the decay of the transcripts. This study demonstrates that TTP plays a critical role in EMT process. Overexpression of TTP in ovarian cancer cells decreased the expression of mesenchymal markers (N-cadherin and Vimentin), increased the expression of epithelial marker (E-cadherin), and inhibited cell migration and invasion activities. On the contrary, inhibition of TTP by siRNA decreased the expression of E-cadherin, increased the expression of N-cadherin and Vimentin, and promoted cell migration and invasion. The cDNA microarray analysis revealed that Twist1 was significantly down-regulated in TTP-overexpressed cells. Twist1 mRNA contains ARE within its 3′-UTR and TTP enhances the decay of Twist1 mRNA through binding to its 3′-UTR. In addition, TTP directly bound to the ARE of Twist1 mRNA by EMSA assay. Ectopic expression of Twist1 gene without 3′UTR blocked the inhibitory of TTP on the EMT. We also observed enhanced levels of Twist1 and reduced TTP levels in human ovarian adenocarcinoma. Collectively, our data indicate that TTP conducts anti-metastatic activity by down-regulating Twist1, presenting a novel mechanism of TTP-mediated regulation of tumor metastasis. Citation Format: Wha Ja Cho, Nal Ae Yoon, Mai-Tram Vo, Young Joo Min, Jeong Woo Park. Tristetraprolin inhibits Twist1-induced cancer cell migration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1126. doi:10.1158/1538-7445.AM2014-1126