Several studies have suggested that p38 MAPK plays an important role in prostate cancer, breast cancer, bladder cancer, liver cancer, lung cancer, transformed follicular lymphoma, and leukemia. Therefore, the relevance of the p38 MAPK pathway in the context of tumor formation has yet to be investigated. The activation of p38 MAPKs has been reported to contribute to the epithelial-mesenchymal transition (EMT) of cells in the primary tumor, to the acquisition of invasion and migrating capabilities, and to the extravasation of migrating tumor cells. In contrast, p38 MAPK inhibition has been correlated with the resistance to anoikis, which allows circulating cancer cells to survive. Tumor cell dormancy has been associated with high p38 MAPK activity in combination with low activity of the ERK1/2 pathway. Analysis of the phenotype of mice disrupted in both the MEK3 and MEK6 genes and the p38α gene has led to the suggestion that p38 can function as a tumor suppressor. The transforming potential of oncogenes is increased in fibroblasts from these animals as well as their tumorigenic potential in nude mice. Suppression of p38 function also plays a critical role in Ras-induced transformation. The tumor suppressive effects of p38 are involved in both the activation of p53 and in p53-induced apoptosis and acts as negative regulator of cell cycle progression. p38 is also activated by oncogenic stresses and plays an important role in Ras-induced senescence in mouse embryo fibroblasts. Overall, it suggests that decreasing p38 activity plays an important role in cancer. The significance of p38 MAPKs in controlling cellular responses to the environment and in regulating gene expression, cell growth, and apoptosis has made them a priority for research related to many human diseases. Therefore, p38 MAPK signaling pathways appear to be a distinguished molecular feature as molecular targets for drug development, and inhibitors of MAPKs will undoubtedly be one of the next groups of drugs developed for the treatment of different solid tumors of the prostate, breast, bladder, liver, and lungs.
Koul H K, Pal M, Koul S. Role of p38 MAP kinase signal transduction in solid tumors[J]. Genes & cancer, 2013: 1947601913507951.