Epithelial-mesenchymal Transition---A Hallmark of Breast Cancer Metastasis

Abstract

Epithelial-mesenchymal transition (EMT) is a highly conserved cellular program that converts polarized, immotile epithelial cells to migratory mesenchymal cells. In addition, EMT was initially recognized as a key step for morphogenesis during embryonic development. Emerging evidences indicate that this important developmental program promotes metastasis, drug resistance, and tumor recurrence, features that are associated with a poor clinical outcome for patients with breast cancer. Therefore, better understanding of regulation and signaling pathways in EMT is essential to develop novel targeted therapeutics. In this review, we present updated developments underlying EMT in tumor progression and metastasis, and discuss the challenges remaining in breast cancer research.

Keywords: EMT; Signaling pathway; Snail; breast cancer; metastasis.

Figure 1. Embryonic signaling pathways lead to induction of EMT and cancer metastasis

TGF-β, Wnt, Notch, RTKs and TNF-α signaling pathways can activate EMT regulators, such as Snail, Slug, Twist, ZEB1 and ZEB2, driving immotile epithelial cells to acquire more invasive phenotypes. EMT bestows tumor cells with stem cell-like characters and resistance to escape immune surveillance and senescence as well as offer survivability against chemo- and endocrine therapies during metastasis.