Tristetraprolin suppresses the EMT through the down-regulation of Twist1 and Snail1 in cancer cells

Abstract

// Nal Ae Yoon 1 , Hyun Gun Jo 1 , Unn Hwa Lee 1 , Ji Hye Park 1 , Ji Eun Yoon 1 , Jinhyun Ryu 2 , Sang Soo Kang 2 , Young Joo Min 3 , Seong-A Ju 4 , Eun Hui Seo 5 , In Young Huh 5 , Byung Ju Lee 1 , Jeong Woo Park 1 , Wha Ja Cho 4 1 Department of Biological Sciences, University of Ulsan, Ulsan 680–749, Korea 2 Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Korea 3 Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea 4 Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea 5 Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682–060, Korea Correspondence to: Jeong Woo Park, e-mail: jwpark@ulsan.ac.kr Wha Ja Cho, e-mail: wjcho26@ulsan.ac.kr Keywords: tristetraprolin, EMT, Twist1, Snail1, cell migration Received: August 20, 2015      Accepted: January 17, 2016      Published: January 31, 2016 ABSTRACT Inhibition of epithelial-mesenchymal transition (EMT)-inducing transcription factors Twist and Snail prevents tumor metastasis but enhances metastatic growth. Here, we report an unexpected role of a tumor suppressor tristetraprolin (TTP) in inhibiting Twist and Snail without enhancing cellular proliferation. TTP bound to the AU-rich element (ARE) within the mRNA 3′UTRs of Twist1 and Snail1 , enhanced the decay of their mRNAs and inhibited the EMT of cancer cells. The ectopic expression of Twist1 or Snail1 without their 3′UTRs blocked the inhibitory effects of TTP on the EMT. We also observed that TTP overexpression suppressed the growth of cancer cells. Our data propose a new model whereby TTP down-regulates Twist1 and Snail1 and inhibits both the EMT and the proliferation of cancer cells.