Figure 1

Epithelial-mesenchymal transition and stem cell traits in breast cancer progression. Breast tumors may originate from the transformation of normal adult tissue stem cells or from more differentiated progenitors that have acquired self-renewal capabilities (left panel). Moreover, a subset of resident mammary gland stem cells (MaSCs, in blue) exhibit epithelial-mesenchymal transition (EMT) features a priori. The EMT features of metaplastic and claudin-low breast tumors may thus signify either that they derive from cells that have undergone EMT or that they originate from deregulated expansion of a pre-existing stem cell pool that expresses EMT-associated markers. Additionally, the induction of sporadic EMT within a tumor bestows migratory and invasive potential coupled with self-renewal capabilities to cancer cells, generating cancer stem cells (CSCs) (right panel). Following extravasation and upon encountering an altered local microenvironment, CSCs (in red) may at least partially revert to an epithelial phenotype (mesenchymal-epithelial transition (MET)) to allow adhesion and proliferation at distal sites. As sporadic EMT and MET are triggered by extracellular stimuli and microenvironment factors, this model provides a plausible explanation for the de novo generation of CSCs from differentiated tumor cells and suggests that passage through EMT and MET is an alternative and/or additional driving force in breast tumorigenesis.