Grant: Operating Grant

In normal healthy organisms cell proliferation is carefully controlled and the effects of oncongenic stimuli are neutralized by cellular tumor suppressor responses. We have discovered that a cellular signaling pathway known best for conveying proliferation signals in tumors can mediate antitumor responses as well. Here we propose to dissect the mechanisms of tumor suppression carry out by the extracellular regulated kinases 1 and 2 (ERK1 and 2). At the cellular levels the ERK pathway is essential to carry out the process of oncogene induced senescence, a permanent cell cycle arrest that prevents tumor formation. Senescence is the mechanism that keeps benign tumors harmless and can be activated in malignant tumors by chemotherapy. By unrevealing the molecular mechanisms by which ERK1/2 regulates senescence we can identify cellular targets for new cancer therapeutics.