|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Onder, TT, Gupta, PB, Mani, SA, Yang, J, Lander, ES, Weinberg, RA|
|Date Published||2008 May 15|
|Keywords||Animals, 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 Journal||Cancer Res.|
|Grant List||R01-CA078461 / CA / NCI NIH HHS / United States|