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Oncotarget. 2016 Feb 23;7(8):8931-43. doi: 10.18632/oncotarget.7094.

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

Author information

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.

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.

KEYWORDS:

EMT; Snail1; Twist1; cell migration; tristetraprolin

PMID:
26840564
PMCID:
PMC4891015
DOI:
10.18632/oncotarget.7094
[Indexed for MEDLINE]
Free PMC Article

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