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. 2017 Feb 23;2(4):e87489. doi: 10.1172/jci.insight.87489

Figure 8. Tumor-surrounding adipocytes promote a metabolic remodeling in breast cancer cells, leading to increased aggressiveness.

Figure 8

Tumor secretions induce a lipolytic process in surrounding adipocytes, which then become cancer-associated adipocytes (CAA). The large quantities of free fatty acids (FFAs) released after adipocyte activation are uptaken and stored as triglycerides (TG) by cancer cells. In these cells, adipose triglyceride lipase (ATGL) overexpression activates a lipolytic process, leading to the release of FFA from lipids droplets and their translocation into mitochondria via the carnitine palmitoyltransferase 1A (CPT1A). The massive influx of lipids induces uncoupled fatty acid oxidation (FAO), characterized by uncoupling protein 2 (UCP2) and inhibitory factor 1 (IF1) overexpression and decreased ATP levels. The reduced ATP content activates AMPK, which promotes both mitochondrial biogenesis and FFA uptake into mitochondria via the acetyl-CoA carboxylase (ACC) inhibition. This circle maintains the metabolic remodeling of tumor cells and increases their aggressiveness.