Epithelial-to-Mesenchymal Transition Signaling Pathways Responsible for Breast Cancer Metastasis.

Abstract

Breast carcinoma is highly metastatic and invasive. Tumor metastasis is a convoluted and multistep process involving tumor cell disseminating from their primary site and migrating to the secondary organ. Epithelial-mesenchymal transition (EMT) is one of the crucial steps that initiate cell progression, invasion, and metastasis. During EMT, epithelial cells alter their molecular features and acquire a mesenchymal phenotype. The regulation of EMT is centered by several signaling pathways, including primary mediators TGF-β, Notch, Wnt, TNF-α, Hedgehog, and RTKs. It is also affected by hypoxia and microRNAs (miRNAs). All these pathways are the convergence on the transcriptional factors such as Snail, Slug, Twist, and ZEB1/2. In addition, a line of evidence suggested that EMT and cancer stem like cells (CSCs) are associated. EMT associated cancer stem cells display mesenchymal phenotypes and resist to chemotherapy or targeted therapy. In this review, we highlighted recent discoveries in these signaling pathways and their regulation in breast cancer metastasis and invasion. While the clinical relevance of EMT and breast cancers remains controversial, we speculated a convergent signaling network pivotal to elucidating the transition of epithelial to mesenchymal phenotypes and onset of metastasis of breast cancer cells.