Grant: Operating Grant

Physiological cell death widely occurs through induction of a cell suicide program called apoptosis. Apoptosis provides a self-cellular defense against detrimental assaults and also against aberrant cellular growth that leads to cancer, by eliminating cells bearing anomalies. Acquired resistance to apoptosis is a hallmark of human tumors and contributes to the resistance of these cells to many anti-cancer agents. Other modes of cell death also exist, but the molecular mechanisms are poorly understood. Furthermore, a number of viral and cellular proteins have been identified, which possess the remarkable ability to destroy cancer cells, while sparing normal cells. Hence, these products seem to activate novel modes of cell death that operate selectively in cancer cells, by sensing and exploiting critical lesions common to cancer cells. This research program aims to comprehend how one of these cancer cell-selective killers, the viral protein named E4orf4, functions at the molecular level. We found that E4orf4 interferes with cellular functions that are deregulated during cell transformation and that depend on key enzymes (Src tyrosine kinases) participating to cancer progression. The study of the mode of action of E4orf4, in cancer cells and in mouse models, could help developing new anti-cancer agents that would be more efficient and less toxic to normal cells.