Biochem Biophys Res Commun. 2014 Sep 24. pii: S0006-291X(14)01695-7. doi: 10.1016/j.bbrc.2014.09.069. [Epub ahead of print]

Breast Cancer Stem Cells, EMT and Therapeutic Targets.

Kotiyal S¹, Bhattacharya S².

Abstract

A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells(BCSCs) exhibit great phenotypical plasticity which allows them to undergo "epithelial to mesenchymal transition" (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-β, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, Nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and Syndecan which can be targeted for therapeutic achievements.