A new study finds that p38-alpha MAPK can sense oxidative stress in cells and respond by inhibiting tumor formation. The research, published in the February issue of the journal Cancer Cell, published by Cell Press, provides exciting new insight into the specific mechanisms by which suppresses the development of cancer and identifies possible targets for development of new anticancer therapeutics.
The MAPK p38-alpha is a signaling protein that plays a critical role in coordinating cellular responses to stress, including oxidative stress that is characterized by the accumulation of increased levels of reactive oxygen species (ROS) within the cell. Although the p38-alpha pathway has been implicated in tumor suppression, the mechanisms involved are not well understood. Dr. Angel R. Nebreda from CNIO (Spanish National Cancer Center) in Madrid and colleagues induced malignant transformation in cells from mice lacking p38-alpha and in wild-type cells to study the importance of p38-alpha in tumorigenesis.
The deficiency of p38-alpha caused increased cell proliferation, decreased cell death via apoptosis, and enhancement of other characteristics associated with malignancy. Importantly, reintroduction of p38-alpha to the deficient cells reversed this phenotype. The researchers observed that the transformed cells lacking p38-alpha had much higher ROS levels than the wild-type cells. Further, ROS-stimulated p38-alpha activity in the wild-type cells stimulated apoptosis, whereas the cells lacking p38-alpha were resistant to ROS-induced apoptosis. The researchers point out that this finding may have clinical significance, as they observed that increased ROS levels were also linked to tumorigenic potential in several human cancer cell lines that were examined.
The authors suggest that it may be possible for cancer cells to escape the tumor-suppressive functions of p38-alpha by desensitizing p38-alpha to oxidative stress. Indeed, many tumor cell
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Contact: Erin Doonan
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617-397-2802
Cell Press
12-Feb-2007