Small Molecules, Big Problem
By Michael Balter, ScienceNOW Daily News, 26 September 2007
sciencenow.sciencemag.org
A new study has found that a tiny molecule can trigger breast cancer cells to go on an invasive rampage. The molecule might be a potential target for new therapies.
Small pieces of RNA called microRNAs help control gene activity and orchestrate development in plants and animals (ScienceNOW, 8 July 2002). But these essential molecules can also turn nefarious: Some of them apparently cause cancer. How they do so is poorly understood, although recent studies have suggested that many microRNAs originate in regions of the human genome associated with cancer risk.
A team led by cancer researcher Robert Weinberg of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, set out to track the involvement of microRNAs in the spread, or metastasis, of breast cancer cells. In a screen of 29 microRNAs previously implicated in breast cancer, the team identified one--called miR-10b--that was prevalent in a very aggressive human breast cancer cell line but not in sedentary tumor cells. When the researchers blocked the action of miR-10b, the invasiveness of these cells declined 10-fold. And when the scientists introduced miR-10b into a culture of nonmetastatic breast cancer cells, they became highly invasive, as measured by their ability to migrate through a filter into a layer of target cells.
The team then implanted miR-10b-making cells into the mammary area of young female mice. After 6 weeks, the cells had begun to spread to distant tissues such as the lungs; nonmetastatic cells, by contrast, caused breast tumors but did not spread. Finally, the researchers traced the genetic pathways that influence the regulation and action of miR-10b. They found that the molecule's production is under the control of a gene called Twist, which had previously been identified as a "master regulator" of embryonic development. In turn, miR-10b influences the expression of two other genes involved in cell migration and cancer formation. The scientists report their findings online 26 September in Nature.
Weinberg and his colleagues caution that despite the importance of miR-10b in triggering the spread of breast cancer cells, it is unclear whether their findings will lead to new therapies. "Although it is likely, we cannot yet conclude that targeting miR-10b will reverse metastasis," says the paper's lead author, Whitehead cancer researcher Li Ma. But other scientists are more optimistic. "The work was impeccably performed," says developmental biologist and pioneer in microRNA research Frank Slack of Yale University. "The therapeutic potential ... is immense and very worthwhile pursuing." Carlo Croce, a cancer geneticist at Ohio State University in Columbus, agrees that the findings "are very important and may provide a potentially important target for treatment." |
