XBP1 induces snail expression to promote epithelial- to-mesenchymal transition and invasion of breast cancer cells

Breast cancer is highly metastatic disease and the most lethal of the gynecologic malignancies. Epithelial-to-mesenchymal is a crucial process for the invasion of epithelial tumors. Recent studies revealed that breast cancer cells that have undergone EMT acquire aggressive malignant properties, but the molecular mechanisms underlying this transition are not well-understood. In this study, we report findings that human X-box binding protein1 (XBP1) acts as a novel regulator of EMT. We found that increased expression of XBP1 was associated with the progression of breast cancer and that XBP1 protein was significantly over-expressed in matched metastatic tumor. High XBP1 protein also predicts shorter overall survival of breast cancer patients. RNA interference-mediated knockdown of XBP1 expression restored E-cadherin expression and cell-cell junction formation in breast cancer cells, suppressing cell invasion, and tumor formation. In contrast, overexpression of XBP1 decreased the expression of the epithelial marker E-cadherin but increased the mesenchymal markers in breast cancer cells. Our finding demonstrates the upregulated expression of the key EMT regulator Snail and that it mediated EMT activation and cell invasion by XBP1.