Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers.

A distinct group of breast cancers, called "basal" or "triple-negative" (TN) cancers express both basal cytokeratins and the epidermal growth factor receptor, but fail to express estrogen receptors, progesterone receptors or HER2 and have stem-like or mesenchymal features. They are particularly aggressive, are frequently chemo-resistant, with p53 mutation, up-regulation of IL-6 and Stat3. Because TN cells are particularly sensitive to the anti-diabetic agent metformin, we hypothesized that it may target JAK2/Stat3 signaling.