[OT] Small Molecules, Big Problem

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Small Molecules, Big Problem

By Balter

ScienceNOW Daily News

26 September 2007

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 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 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. "

http://sciencenow.sciencemag.org/cgi/content/full/2007/926/1?etoc