| First Author | Doerner SK | Year | 2016 |
| Journal | Mol Cancer Res | Volume | 14 |
| Issue | 10 | Pages | 953-965 |
| PubMed ID | 27535705 | Mgi Jnum | J:236248 |
| Mgi Id | MGI:5805586 | Doi | 10.1158/1541-7786.MCR-16-0153 |
| Citation | Doerner SK, et al. (2016) High-Fat Diet-Induced Complement Activation Mediates Intestinal Inflammation and Neoplasia, Independent of Obesity. Mol Cancer Res 14(10):953-965 |
| abstractText | Obesity and related metabolic disturbances are closely associated with pathologies that represent a significant burden to global health. Epidemiological and molecular evidence links obesity and metabolic status with inflammation and increased risk of cancer. Here, using a mouse model of intestinal neoplasia and strains that are susceptible or resistant to diet-induced obesity, it is demonstrated that high-fat diet-induced inflammation, rather than obesity or metabolic status, is associated with increased intestinal neoplasia. The complement fragment C5a acts as the trigger for inflammation and intestinal tumorigenesis. High-fat diet induces complement activation and generation of C5a, which in turn induces the production of proinflammatory cytokines and expression of proto-oncogenes. Pharmacological and genetic targeting of the C5a receptor reduced both inflammation and intestinal polyposis, suggesting the use of complement inhibitors for preventing diet-induced neoplasia. IMPLICATIONS: This study characterizes the relations between diet and metabolic conditions on risk for a common cancer and identifies complement activation as a novel target for cancer prevention. Mol Cancer Res; 14(10); 953-65. (c)2016 AACR. |
