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MicroRNAs, EMT and Cancer Progression

03/31/2008

In the April 1 issue of G&D, a research team led by Dr. Marcus Peter (University of Chicago) identifies the microRNA miR-200 as both a powerful indicator and regulator of the epithelial phenotype of cancer cells.

EMT (the epithelial-to-mesenchymal transition) is the conversion of an epithelial cell into a mesenchymal cell. Morphologically, EMT is characterized by a loss of cell adhesion and increased cell motility. At a molecular level, it is characterized by a decreased expression of the cell adhesion molecule and epithelial marker, E-cadherin, and an increased expression of the intermediate filament protein and mesenchymal cell marker, Vimentin.

EMT is a normal embryological process, but it is implicated in various adult pathologies including cancer metastasis.

Dr. Peter and colleagues analyzed 60 different cell lines from the National Cancer Institute, representing 9 different types of human cancers, and found that miR-200 is a consistent marker of cells that express E-cadherin but lack Vimentin. This was confirmed for primary ovarian cancer.

The researchers went on to show that miR-200 targets the transcriptional repressors of E-cadherin, ZEB1 and ZEB2, and that altering miR-200 levels in established cancer cell lines induced changes consistent with either inducing EMT or the reverse process, MET. Thus, in the context of cancer progression, decreased miR-200 expression increases ZEB1/2 activity, represses E-cadherin levels, and ultimately induces EMT.

"We expected an important process of cellular differentiation such as EMT to be regulated by microRNAs but were surprised by the extraordinarily tight control of EMT by miR-200 through the ZEB proteins. Our ability to reverse EMT by reintroducing miR-200 into cancer cells gives rise to the hope that this miRNA family might be useful in reversing cancer progression" explains Dr. Peter.


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