A team of scientists at the Salk Institute for Biological Studies uncovered a pathway that the tumor-suppressor protein LKB1 uses to halt cell growth when nutrients are low.
Previously, researchers showed that AMPK’s growth-slowing function is directed by the protein LKB1. The loss of LKB1 has been correlated with the formation of benign growths, called hamartomas, and some types of malignant lung and colon cancer. Many of these tumors showed very high levels of unregulated mTOR activity, a growth-promoting protein.
In the current study, scientists combed through collections of protein fragments biochemically phosphorylated by AMPK and found one corresponding to a novel candidate, raptor. Using mouse and human cells, the researchers observed that AMPK attaches a chemical phosphate group to raptor in response to energy stress. As a result, raptor doesn’t function properly, inactivating mTOR and halting cell division.
The investigators also say that their work hints at another clinical association: The type 2 diabetes drug metformin activates AMPK, suggesting that the LKB1/AMPK pathway is a molecular link between diabetes and cancer. “This circuit could in part explain the increased cancer risk seen in type 2 diabetic patients,” says Reuben Shaw, Ph.D., assistant professor in the Molecular and Cell Biology Laboratory of the Dulbecco Center for Cancer Research and leader of the study. He notes that many are predisposed to breast, prostate, or colon cancer.
The study will be published in the April 25 issue of Molecular Cell.