Tristetraprolin suppresses the EMT through the down-regulation of Twist1 and Snail1 in cancer cells
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Nal Ae Yoon1, Hyun Gun Jo1, Unn Hwa Lee1, Ji Hye Park1, Ji Eun Yoon1, Jinhyun Ryu2, Sang Soo Kang2, Young Joo Min3, Seong-A Ju4, Eun Hui Seo5, In Young Huh5, Byung Ju Lee1, Jeong Woo Park1, Wha Ja Cho4
1Department of Biological Sciences, University of Ulsan, Ulsan 680–749, Korea
2Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Korea
3Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea
4Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea
5Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682–060, Korea
Jeong Woo Park, e-mail: [email protected]
Wha Ja Cho, e-mail: [email protected]
Keywords: tristetraprolin, EMT, Twist1, Snail1, cell migration
Received: August 20, 2015 Accepted: January 17, 2016 Published: January 31, 2016
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.
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