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锌指蛋白683通过下调癌细胞中的Twist1和Snail1来抑制上皮-间质转化。

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

作者信息

Yoon Nal Ae, Jo Hyun Gun, Lee Unn Hwa, Park Ji Hye, Yoon Ji Eun, Ryu Jinhyun, Kang Sang Soo, Min Young Joo, Ju Seong-A, Seo Eun Hui, Huh In Young, Lee Byung Ju, Park Jeong Woo, Cho Wha Ja

机构信息

Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.

Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Korea.

出版信息

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

DOI:10.18632/oncotarget.7094
PMID:26840564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4891015/
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.

摘要

抑制上皮-间质转化（EMT）诱导转录因子Twist和Snail可预防肿瘤转移，但会增强转移瘤生长。在此，我们报告了肿瘤抑制因子锌指蛋白36（TTP）在抑制Twist和Snail方面的意外作用，且不会增强细胞增殖。TTP与Twist1和Snail1的mRNA 3'非翻译区（UTR）内的富含AU元件（ARE）结合，增强其mRNA的降解并抑制癌细胞的EMT。不含3'UTR的Twist1或Snail1的异位表达阻断了TTP对EMT的抑制作用。我们还观察到TTP过表达抑制癌细胞生长。我们的数据提出了一种新模型，即TTP下调Twist1和Snail1并抑制癌细胞的EMT和增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/6086f77dee73/oncotarget-07-8931-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/69384283c2bd/oncotarget-07-8931-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/2d2bd2e4a64f/oncotarget-07-8931-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/8fce36ba3143/oncotarget-07-8931-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/7e45a9513046/oncotarget-07-8931-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/0b0bd7dc0d2f/oncotarget-07-8931-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/956f49564709/oncotarget-07-8931-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/6086f77dee73/oncotarget-07-8931-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/69384283c2bd/oncotarget-07-8931-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/2d2bd2e4a64f/oncotarget-07-8931-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/8fce36ba3143/oncotarget-07-8931-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/7e45a9513046/oncotarget-07-8931-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/0b0bd7dc0d2f/oncotarget-07-8931-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/956f49564709/oncotarget-07-8931-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dc/4891015/6086f77dee73/oncotarget-07-8931-g007.jpg

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