Dedifferentiation and metabolic reprogramming of human adipocytes in the tumor niche triggered by colorectal cancer cells

Tumor development and formation are primarily influenced by the interactions of surrounding tissues, and the cells of these become incorporated into the vicinity of the tumor and shape its microenvironment. In particular, adipose tissue plays a pivotal role, and its primary cellular components, adipocytes, make a significant contribution to this process. The multifaceted role of fat cells in the formation and progression of cancer remains an active area of research, and many aspects of this process remain undefined. Thus, the main objective of this study was to investigate how colorectal cancer (CRC) cells influence human-derived adipocytes reprogramming. Our results demonstrate that CRC cells promote the dedifferentiation of adipocytes into a more fibroblast-like phenotype, and this process resulted in the formation of cells with characteristics resembling those of cancer-associated adipocytes (CAAs). Furthermore, co-culture with cancer cells disrupted cytoskeletal homeostasis in adipocytes, which enhanced the formation of actin filaments and led to the development of a more complex vimentin network. This was accompanied by alterations in lipid droplet profiles and the levels of proteins involved in lipid storage and metabolism. Interestingly, CRC cells also modulated the metabolic activity of CAAs and affected their mitochondrial distribution and dynamics. The results underscore the substantial influence of CRC cells on adipocytes, which may have an essential role in their recruitment into the tumor niche and protumorigenic activity.