Spatiotemporal Regulation of Epithelial-Mesenchymal Transition Is Essential for Squamous Cell Carcinoma Metastasis

SummaryEpithelial-mesenchymal transition (EMT) is implicated in converting stationary epithelial tumor cells into motile mesenchymal cells during metastasis. However, the involvement of EMT in metastasis is still controversial, due to the lack of a mesenchymal phenotype in human carcinoma metastases. Using a spontaneous squamous cell carcinoma mouse model, we show that activation of the EMT-inducing transcription factor Twist1 is sufficient to promote carcinoma cells to undergo EMT and disseminate into blood circulation. Importantly, in distant sites, turning off Twist1 to allow reversion of EMT is essential for disseminated tumor cells to proliferate and form metastases. Our study demonstrates in vivo the requirement of “reversible EMT” in tumor metastasis and may resolve the controversy on the importance of EMT in carcinoma metastasis.

► Twist1 is sufficient to promote EMT and invasive tumor progression in vivo
► Twist1 promotes carcinoma cell intravasation and extravasation in vivo
► Induction of Twist1 and EMT reduces tumor cell proliferation
► Reversion of EMT is essential for establishing macrometastases