Although it is well established that the epithelial-mesenchymal transition (EMT) generates cells with properties of stem cells, the molecularmechanisms responsible for this change remain largely undefined. We set out to identify the mechanisms by examining the expression of stem cell markers as well as microRNAs in MCF-10A cells during EMT induction. By immunostaining and FACS analysis, we found that during EMT induction by either TGF-β treatment or overexpression of KLF8, both the expression of CD44high/CD24low and the activity of aldehyde dehydrogenase (ALDH) were dramatically increased. Using microRNA PCR array, we identified a microRNA signature associated with the EMT. Using microRNA inhibitor, We further demonstrated that one of the microRNAs, miR-146a, is upregulated and plays an important role in keeping the stem cell percentage during EMT induced by both TGF-β and KLF8, as revealed by manipulation of miR-146a expression, analysis of the stem cell markers and mammosphere growth. Taken together, these results highlight a novel role for miR-146a in regulating the stem-like cell induction from MCF-10A cells by EMT. Experiments are in progress to investigate the contribution of KLF8-regulated expression of miR146a and its targets to the stem cell induction and transformation. Supported by: NIH, ACS, Komen and NYSTEM grants to J.Z.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-24.