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Winter 2017


cancer; cell biology


Although considerable evidence shows that the drug metformin, used for more than 50 years to treat type 2 diabetes, can prevent or slow the growth of certain cancers, the mechanism behind these anticancer effects has been unknown. Recently, however, a team of HMS researchers at Massachusetts General Hospital has identified a pathway that appears to underlie metformin’s ability to both block the growth of human cancer cells and extend the lifespan of the roundworm Caenorhabditis elegans, findings indicating that this single genetic pathway plays an important role in a wide range of organisms.

“We found that metformin reduces the traffic of molecules into and out of the cell’s nucleus,” says Alexander Soukas, an HMS assistant professor of medicine and senior author of the paper published in the December 15, 2016, issue of Cell. “Reduced nuclear traffic translates into the ability of the drug to block cancer growth. Remarkably, this reduced traffic is also responsible for metformin’s ability to extend lifespan.”

Metformin helps lower blood glucose in patients with type 2 diabetes by reducing the liver’s ability to produce glucose for release into the bloodstream, possibly by blocking the activity of mitochondria, structures that fuel cellular activity.

Soukas and colleagues found that metformin’s action against breast, prostate, and pancreatic cancers relies on two elements of a single genetic pathway—the nuclear pore complex—which allows the passage of molecules into and out of the nucleus, and an enzyme called ACAD10.

“Our experiments showed two important things,” says Soukas, who is also a faculty member of the Mass General Center for Genomic Medicine. “If we force the nuclear pore to remain open or if we permanently shut down ACAD10, metformin can no longer block the growth of cancer cells. That suggests that the nuclear pore and ACAD10 may be manipulated in specific circumstances to prevent or even treat certain cancers.”      

Image: Theasis/Getty Images

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