| First Author | Yin N | Year | 2016 |
| Journal | Oncogene | Volume | 35 |
| Issue | 8 | Pages | 1039-48 |
| PubMed ID | 25961922 | Mgi Jnum | J:301882 |
| Mgi Id | MGI:6507264 | Doi | 10.1038/onc.2015.158 |
| Citation | Yin N, et al. (2016) p38gamma MAPK is required for inflammation-associated colon tumorigenesis. Oncogene 35(8):1039-48 |
| abstractText | Chronic inflammation has long been considered to causatively link to colon cancer development. However, signal transduction pathways involved remain largely unidentified. Here, we report that p38gamma mitogen-activated protein kinase mediates inflammatory signaling to promote colon tumorigenesis. Inflammation activates p38gamma in mouse colon tissues and intestinal epithelial cell-specific p38gamma knockout (KO) attenuates colitis and inhibits pro-inflammatory cytokine expression. Significantly, p38gamma KO inhibits tumorigenesis in a colitis-associated mouse model. The specific p38gamma pharmacological inhibitor pirfenidone also suppresses pro-inflammatory cytokine expression and colon tumorigenesis. The tumor-promoting activity of epithelial p38gamma was further demonstrated by xenograft studies. In addition, p38gamma is required for beta-catenin/Wnt activities and p38gamma stimulates Wnt transcription by phosphorylating beta-catenin at Ser605. These results show that p38gamma activation links inflammation and colon tumorigenesis. Targeting p38gamma may be a novel strategy for colon cancer prevention and treatment. |
