| First Author | Singh S | Year | 2020 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1866 |
| Issue | 5 | Pages | 165660 |
| PubMed ID | 31891805 | Mgi Jnum | J:293968 |
| Mgi Id | MGI:6450620 | Doi | 10.1016/j.bbadis.2019.165660 |
| Citation | Singh S, et al. (2020) Role of TNFalpha and leptin signaling in colon cancer incidence and tumor growth under obese phenotype. Biochim Biophys Acta Mol Basis Dis 1866(5):165660 |
| abstractText | Epidemiological studies over the last few decades have shown a strong influence of obesity on colon cancer risk and its progression. These studies have primarily focussed on the role of adipokines in driving cancer progression. We investigated the incidence of cancerous polyp formation and tumor progression in presence and absence of functional leptin along with exploring the role of tumor necrosis factor alpha (TNFalpha), under obese condition. By utilizing diet induced obese and genetically obese mice, carcinogen induced colon polyp formation was investigated. Experiments were performed using tumor tissues and cell lines to delineate the inter-relationship between leptin and TNFalpha. Data shown in this report indicates that in leptin knockdown obese mice, AOM/DSS induced polyps are smaller and lesser in numbers as compared to AOM/DSS induced polyps in diet induced obese mice. Further in vitro experiments suggest that abrogation of leptin associated pathways promote TNFalpha induced apoptosis. Mechanistically, we report that TNFalpha induces p53 independent cell death through up regulation of p53 upregulated modulator of apoptosis (PUMA). TNFalpha induced PUMA was inhibited upon pre- exposure of cells to leptin, prior to TNFalpha treatment. Collectively these results indicate that obesity due to leptin non-functionality facilitates TNFalpha induced colon cancer cell death. |
