Fig. 4.

Working model schematically depicting how the anti-diabetic drug metformin can alter miRNA-regulated cell differentiation to prevent cancer progression. Inva-sive/metastatic progression of BC can be viewed as a miRNA let-7-regulated continuum of progressive dedifferentiation (i.e. EMT) with a cell at the endpoint that has stem cell-like properties (Peter, 2009). Metformin-enhanced let-7 expression in pre-malignant cells may efficiently push them to become less “embryonic” (i.e. mesenchymal stem-like cells) and more “normal” (non-stem differentiated epithelial cells), thus blocking the dynamic nature of cellular transformation and CSC formation in response not only to oncogenes but also to the stressful local ductal tissue microenvironment.