Human adipocytes support the proliferation and migration of colorectal cancer cells with concomitant modulation of their glycolysis rate and lipid metabolism

Adipose tissue plays a pivotal role in the development and formation of colorectal cancer (CRC). Its primary cellular component, adipocytes, contributes significantly to this process. In the presence of cancer cells, adipocytes convert into cancer-associated adipocytes, which acquire features that promote tumor progression. Thus, the main objective of this study was to investigate how cancer-associated adipocytes stimulate the aggressiveness of CRC cells. Using an indirect co-culture model, we characterized the functional, molecular, and metabolic modifications of CRC cells induced by primary human adipocytes. Our results demonstrate that adipocytes promote an aggressive CRC cell phenotype. Adipocytes stimulated hybrid epithelial-mesenchymal transition of CRC cells with concomitant modification in the expression profile of stem cell markers. Moreover, upon co-culture with adipocytes, the metabolic reprogramming of cancer cells favoring fatty acid oxidation as well as glycolysis linked with cholesterol accumulation was noted. Interestingly, adipocytes also modulated the level of lipases and the lipolysis rate in CRC cells. The results underline the substantial influence of adipocytes on CRC cell behavior, highlighting the presence of several simultaneous mechanisms possibly controlling the tumor expansion in the adipocyte-rich niche.