In the June 1 issue of G&D, Dr. Eileen White and colleagues at Rutgers University/University of Medicine and Dentistry of New Jersey/Cancer Institute of New Jersey, report, for the first time, that the cellular self-digesting process of autophagy can protect genome integrity – lending new insight into the seemingly contradictory roles of autophagy as both a cell survival and tumor suppressor pathway. Using cells that were genetically engineered to lack one copy of a key autophagy gene, Dr. White and colleagues demonstrated that although loss of autophagy reduces tumor cell survival during starvation, the concurrent genome instability could accelerate tumor progression. Thus, the normal function of autophagy sustains, but also protects cells by limiting genome damage during starvation. "Understanding mechanisms by which tumor cells respond to metabolic stress is key to designing therapeutics: in established tumors, autophagy inhibitors may help starve tumor cells to death, while early tumor emergence and progression may be suppressed with autophagy promoters by preventing genome damage," explains Dr. White.
Genes & Development