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Signaling pathways point to vulnerability in breast cancer stem cells
Date:6/9/2011

CAMBRIDGE, Mass. (June 9, 2011) Whitehead Institute researchers have identified signals from breast epithelial cells that can induce those cells to transition to and maintain a mesenchymal and stem cell-like cell state that imbues both normal and cancer cells with a greater ability to migrate and self-renew. Interrupting these signals strips the cells of the migratory, invasive and self-renewal abilities used by cancer stem cells to seed new tumors.

"Stem cells are important in both cancers and normal tissues. On the one hand we'd like to know what creates so-called cancer stem cells in tumors and on the other hand we'd like to know what creates normal stem cells in normal epithelial tissues," says Whitehead Founding Member Robert Weinberg. "We have reason to believe that these two dynamics are orchestrated by a common regulatory machinery. So this work may be applicable for understanding both breast cancer cells and normal epithelial cells, such as the normal cells in the normal mammary ducts."

During an epithelial-to-mesenchymal transition (EMT), epithelial cells acquire the traits of mesenchymal cells. Unlike the tightly-packed epithelial cells that stick to one another, mesenchymal cells are loose and free to move around a tissue. The attributes of mesenchymal cells are beneficial during development, but when hijacked by cancer cells, confer the ability to migrate to distant sites. In addition, the passage through an EMT enables adult cancer cells to seed new tumors with high efficiency, the hallmark trait of cancer stem cells. Although passage through an EMT is recognized as an important step in the formation of cancer stem cells, scientists have been unable to clearly identify the cues in a cell's microenvironment that induce an EMT.

By studying human breast epithelial cells, Christina Scheel, a postdoctoral researcher in the Weinberg lab, pinpointed three signaling pathways (TGF-beta, non-canonical Wnts, and canonical Wnts) t
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Contact: Nicole Giese
giese@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

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