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Protein pushes breast cancer cells to metastasize
Date:7/9/2014

A telling the cell to destroy it, for instance. "These structural differences help determine RNA's fate, by exposing or hiding the binding sites for those key proteins," says Goodarzi.

So Goodarzi and Saeed Tavazoie developed a computer algorithm that scans samples of cancer cells and identifies patterns in the shapes and sequences of RNA. In the current study, the authors applied this algorithm to breast cancer cells. In cells prone to metastasis, for example, the scientists found certain RNA hairpin loops that were overrepresented in the sequences of RNAs targeted for destruction. They then identified a protein that binds to those hairpin sequences TARBP2, known to play a role in the formation of small RNAs known as microRNAs. But here, it appears TARBP2 can also act as a "master regulator" of RNA itself, by binding to multiple sites and causing a suite of changes that lead to metastasis including the destruction of the RNAs that carry those key binding sites. Indeed, they found that TARBP2 is overexpressed in cells prone to metastasizing, as well as in metastatic human breast tumors themselves.

To determine how TARBP2 carries out its effects, the researchers looked at which genes appear to be downregulated in metastatic cell lines, reasoning that TARBP2 may block these disease suppressors. They made two surprising discoveries APP, a protein linked to Alzheimer's disease, and ZNF395, which is associated with Huntington's disease, are both downregulated by TARBP2. Cells prone to metastasis showed higher levels of TARBP2 and lower levels of APP and ZNF395; in cancer cells that tend not to spread throughout the body, the opposite was true.

"This was a surprising finding, because these genes are normally associated with neurodegeneration are now implicated in breast cancer metastasis and progression," says Tavazoie. "It's interesting that these totally disparate disease processes have a potential molecular link. We don't know what that m
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Contact: Franklin Hoke
fhoke@rockefeller.edu
212-327-8998
Rockefeller University
Source:Eurekalert

Page: 1 2 3

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