Journal
CANCER CELL
Volume 22, Issue 6, Pages 725-736Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2012.09.022
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Funding
- American Cancer Society [RSG-09-282-01-CSM]
- UCSD Cancer Center [P30 CA23100]
- NIH [DP2 OD002420-01, T32CA121938]
- Sidney Kimmel Foundation for Cancer Research
- University of California Cancer Research Coordinating Committee
- California Breast Cancer Program postdoctoral fellowship [16FB-0009]
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Epithelial-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.
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