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Scientists Discover Switch That Turns On Metastasis

A specific protein called disabled-2 (Dab2) switches on the process that releases cancer cells from the original tumor and allows the cells to spread and develop into new tumors in other parts of the body, according to a report by scientists from the Cleveland Clinic, Case Western Reserve University, and collaborating institutions. The process called epithelial-mesenchymal transdifferentiation (EMT) has been known to play a role in releasing cells (epithelial cells) on the surface of a solid tumor and transforming them into transient mesenchymal cells, i.e., cells with the ability to migrate and start to grow a new tumor. This is often the fatal process in breast, ovarian, pancreatic, and colorectal cancers. The researchers knew that transforming growth factor beta (TGF-beta) induces EMT, but they did not know how. In their research, they found that TGF-beta triggers the formation of the Dab2 protein and that it is the Dab2 protein that activates the EMT process. Among the group’s findings was that if Dab2 was knocked out in animal models, EMT did not occur. "If we can understand the signaling pathway for modulating EMT, then we can design drugs to delay or halt EMT cells and control tumor progression," said Dr. Gi Jin, one of the authors of the report. This work was published online on February 14, 2010 in Nature Cell Biology. [Press release] [Nature Cell Biology abstract]