Study on senescence-associated tumor promotion

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Cellular senescence was known to be associated with increased levels of reactive oxygen species (ROS), carcinogen known to cause DNA damage. However, molecular mechanisms underlying the increased ROS production has remained unclear. Here, we show that the cross-talk between the p16-RB-pathway and AKT-pathway determines ROS level by controlling the overlapping functions of FoxM1 and FoxO3a, transcription factors known to regulate ROS scavenger expression. We also demonstrate here that this pathway operates not only in cultured fibroblasts but also in mouse liver, indicating that this machinery may contribute broadly to tumorigenesis in vivo.