BREAST CANCER STEM CELL MEDIATED EPITHELIAL-MESENCHYMAL TRANSITION TARGETS: HOPE FOR BREAST CANCER THERAPY

Breast cancer is the most frequently diagnosed disease and one of the leading causes of death among woman worldwide. Treated patients often suffer from disease recurrence and metastasis due to presence of a subset of tumor cells known as breast cancer stem cells (BCSCs). Presence of BCSC is the reason for resistance and failure of therapy due to aberrant activity of aldehyde dehydrogenase, enhanced DNA damage, activation of self renewal signaling pathways and epigenetic deregulations. BCSC is a small cell population originating from normal breast stem cells, having unique characteristics such as self-renewal, high proliferation rate, ability to generate heterogeneity etc. BCSCs demonstrated aberrant activation of highly conserved signaling involved in developmental pathways such as Wnt, Notch and hedgehog as well as RTK, NF-κB and TGF-β signaling. Deregulation of these signaling pathways is frequently linked to epithelial-mesenchymal transition (EMT) which plays an important role in tumor invasion and metastasis by endowing cells with a more motile and invasive phenotype. The current review will focus on aberrant signaling and regulation of EMT in BCSC; and translation of the growing knowledge into development of targeted therapies.