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Cancer Res DOI:10.1158/0008-5472.CAN-07-2938

Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways.

Publication TypeJournal Article
Year of Publication2008
AuthorsOnder, TT, Gupta, PB, Mani, SA, Yang, J, Lander, ES, Weinberg, RA
JournalCancer Res
Date Published2008 May 15
KeywordsAnimals, Cadherins, Cell Communication, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Inbred NOD, Mice, Nude, Mice, SCID, Models, Biological, Neoplasm Metastasis, Signal Transduction, Transcription, Genetic, Twist-Related Protein 1

Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts-an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherin's cell-cell adhesion and intracellular signaling functions. Whereas the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness, and anoikis resistance. We find the E-cadherin binding partner beta-catenin to be necessary, but not sufficient, for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic dissemination by inducing wide-ranging transcriptional and functional changes.


Alternate JournalCancer Res.
PubMed ID18483246
Grant ListR01-CA078461 / CA / NCI NIH HHS / United States