期刊
MOLECULAR CANCER RESEARCH
卷 14, 期 10, 页码 953-965出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-16-0153
关键词
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资金
- Transdisciplinary Research in Energy Balance and Cancer Grant [U54 CA116867, AI030040, AI068730, P40 RR012305]
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. (C) 2016 AACR.
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