A study published in the journal Nature reveals new details about the tumor suppressor PTEN, a gene known to be defective in 2 of every 3 people with uterine cancer and in 30 percent of certain breast and brain cancers.

Led by NYU Langone Medical Center and its Perlmutter Cancer Center, the new study found that PTEN normally protects against cancer by preventing a protein called FBXL2 from tagging another protein for destruction. The tagged protein is IP3R3, a “sensor” that recognizes when a cell is multiplying abnormally, and using up more energy than usual, thereby signaling the abnormal cell to self–destruct.

When PTEN is missing, IP3R3 is tagged for degradation by FBXL2, and this important anticancer safety mechanism is disabled.

PTEN has been the subject of study for years because of its better known role of blocking signals in the PI3K/AKT pathway, a driver of growth and survival in most cancer cell types. The new study describes a second way in which defective PTEN helps to promote cancer.

“FXBL2 may be largely responsible for cancer growth in the many patients with genetic changes that happen to disable PTEN,” says senior study author Michele Pagano, PhD, chair of the Department of Biochemistry and Molecular Pharmacology at NYU Langone. “Our results suggest that tumors with altered PTEN should be treated, not only with PI3k/AKT inhibitors currently in clinical trials, but also with drugs that disable FXBL2, to counter both procancer signals driven by defects in this gene.”

“We also showed that an experimental drug – by itself and in combination with a new form of light therapy – countered FBXL2 to let abnormal cells self–destruct,” says Dr. Pagano, also an investigator with the Howard Hughes Medical Institute.