Adipocytes activate mitochondrial fatty acid oxidation and autophagy to promote tumor growth in colon cancer

• DOI: 10.1038/cddis.2017.21
• Publication Date: 2017-02-02T13:45:39Z
• Authors: Yang-An Wen; Xiaopeng Xing; Jennifer W Harris; Yekaterina Y Zayt...; Mihail I Mitov; Dana L Napier; Heidi L Weiss; B Mark Evers; Tianyan Gao
• Keywords: 0303 health sciences; Fatty Acids; Down-Regulation; Gene Expression; Cell Differentiation; Epithelial Cells; AMP-Activated Protein Kinases; Lipid Metabolism; Coculture Techniques; Cell Line; Mitochondria; 3. Good health; Mice; 03 medical and health sciences; Adipose Tissue; Cell Line, Tumor; Colonic Neoplasms; Adipocytes; Autophagy; Neoplastic Stem Cells; Animals; Humans; Original Article; Oxidation-Reduction

Obesity has been associated with increased incidence and mortality of a wide variety human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate metabolism colon cancer cells remains elusive. In this study, we showed that isolated from adipose tissues patients have an important role in modulating cellular to support tumor growth survival. Abundant were found close association invasive patients. Co-culture led transfer free fatty acids released cells. Uptake allowed survive nutrient deprivation conditions upregulating mitochondrial acid β-oxidation. Mechanistically, co-culture or treating induced autophagy as result AMPK activation. Inhibition attenuated ability utilize blocked growth-promoting effect adipocytes. addition, stimulated expression genes stem downregulated intestinal epithelial cell differentiation primary mouse organoids. Importantly, presence promoted xenograft tumors vivo. Taken together, our results show microenvironment serve energy provider metabolic regulator promote survival