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

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.

SUBMITTER: Yoon NA

PROVIDER: S-EPMC4891015 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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

Yoon Nal Ae NA Jo Hyun Gun HG Lee Unn Hwa UH Park Ji Hye JH Yoon Ji Eun JE Ryu Jinhyun J Kang Sang Soo SS Min Young Joo YJ Ju Seong-A SA Seo Eun Hui EH Huh In Young IY Lee Byung Ju BJ Park Jeong Woo JW Cho Wha Ja WJ

Oncotarget 20160201 8

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 ...[more]

PMID: 26840564

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