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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Electrophoretic Mobility Shift Assay
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Epithelial-Mesenchymal Transition / drug effects*
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Immunoprecipitation
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Luciferases / metabolism
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology*
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Nuclear Proteins / antagonists & inhibitors*
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Nuclear Proteins / genetics
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Snail Family Transcription Factors / antagonists & inhibitors*
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Snail Family Transcription Factors / genetics
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Tristetraprolin / pharmacology*
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Tumor Cells, Cultured
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Twist-Related Protein 1 / antagonists & inhibitors*
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Twist-Related Protein 1 / genetics
Substances
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Nuclear Proteins
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RNA, Messenger
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SNAI1 protein, human
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Snail Family Transcription Factors
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TWIST1 protein, human
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Tristetraprolin
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Twist-Related Protein 1
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Luciferases