The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2

Genes and Development - Tập 22 Số 7 - Trang 894-907 - 2008
Sun-Mi Park1, Arti Gaur2, Ernst Lengyel3, Marcus E. Peter3
1The Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois 60637, USA.
2Dartmouth College,
3The University of Chicago,

Tóm tắt

Cancer progression has similarities with the process of epithelial-to-mesenchymal transition (EMT) found during embryonic development, during which cells down-regulate E-cadherin and up-regulate Vimentin expression. By evaluating the expression of 207 microRNAs (miRNAs) in the 60 cell lines of the drug screening panel maintained by the Nation Cancer Institute, we identified the miR-200 miRNA family as an extraordinary marker for cells that express E-cadherin but lack expression of Vimentin. These findings were extended to primary ovarian cancer specimens. miR-200 was found to directly target the mRNA of the E-cadherin transcriptional repressors ZEB1 (TCF8/δEF1) and ZEB2 (SMAD-interacting protein 1 [SIP1]/ZFXH1B). Ectopic expression of miR-200 caused up-regulation of E-cadherin in cancer cell lines and reduced their motility. Conversely, inhibition of miR-200 reduced E-cadherin expression, increased expression of Vimentin, and induced EMT. Our data identify miR-200 as a powerful marker and determining factor of the epithelial phenotype of cancer cells.

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Tài liệu tham khảo

10.1038/sj.onc.1210508

10.1248/bpb.29.903

10.1038/sj.emboj.7600325

10.1038/sj.onc.1209511

Boyerinas, B. Park, S.M. Shomron, N. Hedegaard, M.M. Vinther, J. Andersen, J.A. Feig, C. Xu, J. Burge, C.B. Peter, M.E. (2008) Identification of Let-7-regulated oncofetal genes. Cancer Res. (in press).

10.1073/pnas.242606799

10.1261/rna.586807

10.1038/sj.onc.1209808

10.1016/S1097-2765(01)00260-X

10.1056/NEJM198612253152606

10.1038/sj.onc.1208429

10.1002/cncr.20946

10.1007/s00428-006-0274-6

Fuchs,, 2002, The prognostic significance of epithelial–mesenchymal transition in breast cancer, Anticancer Res., 22, 3415

10.1158/0008-5472.CAN-06-2698

Gregory, P.A. Bert, A.G. Paterson, E.L. Barry, S.C. Tsykin, A. Farshild, G. Vadas, M.A. Khew-Goodall, Y. Goodall, G.J. (2008) The microRNA-200 family and mir-205 regulate epithelial–mesenchymal transition by targeting the E-cadherin repressors, ZEB1 and SIP1. Nature Cell Biol. (in press).

10.1159/000147748

10.1038/nature03552

10.1172/JCI30487

Hurteau,, 2006, Potential mRNA degradation targets of hsa-miR-200c, identified using informatics and qRT–PCR, Cell Cycle, 5, 1951, 10.4161/cc.5.17.3133

10.1158/0008-5472.CAN-07-1058

10.1038/sj.onc.1210012

10.1007/s10555-006-9006-2

10.1016/j.cell.2005.01.014

10.1158/0008-5472.CAN-07-1083

Maeda,, 2005, Expression of SIP1 in oral squamous cell carcinomas: Implications for E-cadherin expression and tumor progression, Int. J. Oncol., 27, 1535

10.1038/sj.onc.1210436

10.4161/cc.6.21.4845

10.1007/s10495-007-0149-6

10.1387/ijdb.041794hp

10.1038/nrc2131

10.1093/hmg/ddi366

10.1002/ijc.22083

10.1073/pnas.97.12.6391

10.1016/S0002-9440(10)64464-1

10.1038/73432

10.1002/bies.1132

10.1158/0008-5472.CAN-06-1147

10.1002/dvdy.20599

10.1073/pnas.0704372104

10.1091/mbc.E07-03-0249

10.1158/0008-5472.CAN-05-2881

10.1158/0008-5472.CAN-04-0637

10.1038/nrc822

10.1038/nrm1835

10.1016/j.cell.2006.02.037

10.1016/j.ccr.2006.01.025

10.1073/pnas.111614398

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Genes and Development

Tập 22 Số 7

894-907

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