title: Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.
authors.forename: Jeff H
authors.initials: JH
authors.lastname: Tsai
authors.forename: Joana Liu
authors.initials: JL
authors.lastname: Donaher
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Murphy
authors.forename: Sandra
authors.initials: S
authors.lastname: Chau
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1