The p38α MAPK pathway plays key roles in the cellular responses to stress but can also integrate signals that affect many other cellular processes in a cell context-specific and cell type-specific manner. Studies using genetically modified mice have elucidated some in vivo functions for p38α, and provided insights into how this pathway can suppress tumor initiation. There is evidence that cells rely on p38α signaling to engage various tumor suppressor mechanisms, such as cell cycle arrest, apoptosis induction or cell differentiation. Intriguingly, p38α does not seem to be usually mutated in human tumors. On the contrary, it appears that this signaling pathway sometimes can acquire new roles during tumor development, facilitating the proliferation, survival and invasivity of the cancer cells.We are investigating the implication of p38α signaling at different stages of tumor formation, using mouse models of cancer for in vivo studies and cells in culture for mechanistic analysis.