Epithelial-mesenchymal transition in breast cancer progression and metastasis

Abstract

Breast cancer is the most common cancer in women, and approximately 90% of breast cancer deaths are caused by local invasion and distant metastasis of tumor cells. Epithelial-mesenchymal transition (EMT) is a vital process for large-scale cell movement during morphogenesis at the time of embryonic development. Tumor cells usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. Several transcription factors and signals are involved in these events. In this review, we summarize recent advances in breast cancer researches that have provided new insights in the molecular mechanisms underlying EMT regulation during breast cancer progression and metastasis. We especially focus on the molecular pathways that control EMT.

Figure 1.. An overview of signaling networks in controlling epithelial-mesenchymal transition (EMT) and metastasis.

Activation of tumor growth factor-β (TGF-β), Wnt, Notch, receptor tyrosine kinases (RTKs), and tumor necrosis factor-α (TNF-α) signaling pathways leads to the activation of several EMT transcription factors, such as Snail, Slug, and Twist, thus resulting in the induction of EMT. EMT bestows tumor cells with stem cell-like characteristics, resistance to immunosuppression and senescence, and survivability against chemothereapy and endocrine therapy during metastasis.