Epithelial-mesenchymal transition, cancer stem cells and treatment resistance

Abstract

Breast cancer relapse, in a large number of patients, after initial response to standard of care therapy warrants development of novel therapies against recurrent and metastatic cancer. Cancer stem cells (CSCs), present in breast tumors while being intrinsically resistant to conventional therapy, have the ability to self renew and cause tumor recurrence. The residual tumors after therapy, with dramatic enrichment of the CSCs, have all the hallmarks of epithelial- mesenchymal transition (EMT). This review will focus on the link between EMT, CSCs and treatment resistance, since a better understanding of these interactions will allow us to effectively target the residual population after therapy.

Figure 1

Interaction between epithelial-mesenchymal transition and self-renewal pathways of cancer stem cells. ECM, extracellular matrix; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; FGF, fibroblast growth factor; HGF, hepatocyte growth factor; MMP, matrix metalloproteinase; PDGF, platelet-derived growth factor; PDK1, phosphoinositide-dependent kinase-1; PI3K, phosphatidylinositol-3-kinase; SMAD, Sma and Mad-related family; TCF, T-cell factor; TGF, transforming growth factor; VEGFR, vascular endothelial growth factor receptor; ZEB, zinc finger E-box binding homeobox.