title: 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.
authors: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors: Nal Ae
authors: NA
authors: Yoon
authors: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors: Hyun Gun
authors: HG
authors: Jo
authors: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors: Unn Hwa
authors: UH
authors: Lee
authors: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors: Ji Hye
authors: JH
authors: Park
authors: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors: Ji Eun
authors: JE
authors: Yoon
authors: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Korea.
authors: Jinhyun
authors: J
authors: Ryu
authors: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Korea.
authors: Sang Soo
authors: SS
authors: Kang
authors: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea.
authors: Young Joo
authors: YJ
authors: Min
authors: Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea.
authors: Seong-A
authors: SA
authors: Ju
authors: Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea.
authors: Eun Hui
authors: EH
authors: Seo
authors: Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea.
authors: In Young
authors: IY
authors: Huh
authors: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors: Byung Ju
authors: BJ
authors: Lee
authors: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors: Jeong Woo
authors: JW
authors: Park
authors: Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea.
authors: Wha Ja
authors: WJ
authors: Cho
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D051816:Tristetraprolin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D051816:Tristetraprolin; D051879:Twist-Related Protein 1; D008156:Luciferases
keywords: EMT; Snail1; Twist1; cell migration; tristetraprolin