A study in the May 29 issue of Cell has found that cancer cells have an increased reliance on many normal proteins to deal with stress and maintain their deviant state.
Researchers at HMS and Brigham and Women’s Hospital used a technique called RNA interference (RNAi) to knock down the production of thousands of proteins and determine which were particularly necessary for cancer cell survival. They discovered that their experimental tumor cells had a heightened need for dozens of normal proteins and therefore were more vulnerable than normal cells when the underlying genes were turned down.
“Cancer cells actually leverage many genes that don’t harbor mutations to maintain their malignant lifestyles,” said first author and postdoctoral researcher Ji Luo. “These genes probably help them deal with the problems that develop as a result of the continuous presence of growth and survival signaling in tumor cells.”
“Researchers often characterize cancer cells as oncogene addicts, but they’re just as reliant on normal genes that alleviate stress,” explained senior author Stephen Elledge, a Howard Hughes investigator and professor of genetics at HMS and of medicine at Brigham and Women’s Hospital. “These stress management genes deserve attention as potential therapeutic targets.”
In recent years, the National Cancer Institute has supported an ambitious effort to understand the molecular basis of cancer by sequencing cancer genomes. Elledge and Luo are concerned that this Cancer Genome Atlas project will miss the stress management genes.
“If these genes are intact, they won’t stand out when you compare the DNA sequences of cancer cells with normal cells,” said Luo.
Students may contact Stephen Elledge at selledge@genetics.med.harvard.edu for more information.
Conflict Disclosure: The authors declare no conflicts of interest.
Funding Sources: AACR Prevent Cancer Foundation AstraZeneca Fellowship in Translational Lung Cancer Research; Howard Hughes Medical Institute; National Institutes of Health; Department of Defense; Damon Runyon Cancer Research Foundation; Susan G. Komen for the Cure Foundation; and DF/HCC Lung Cancer SPORE grant. The content of the work is the responsibility solely of the authors.
