Obesity Suppresses Cell-Competition-Mediated Apical Elimination of RasV12-Transformed Cells from Epithelial Tissues

Recent studies have revealed that newly emerging transformed cells are often eliminated from epithelial tissues via cell competition with the surrounding normal epithelial cells. This cancer preventive phenomenon is termed epithelial defense against cancer (EDAC). However, it remains largely unknown whether and how EDAC is diminished during carcinogenesis. In this study, using a cell competition mouse model, we show that high-fat diet (HFD) feeding substantially attenuates the frequency of apical elimination of RasV12-transformed cells from intestinal and pancreatic epithelia. This process involves both lipid metabolism and chronic inflammation. Furthermore, aspirin treatment significantly facilitates eradication of transformed cells from the epithelial tissues in HFD-fed mice. Thus, our work demonstrates that obesity can profoundly influence competitive interaction between normal and transformed cells, providing insights into cell competition and cancer preventive medicine. [Display omitted] •High-fat diet (HFD) feeding suppresses extrusion of transformed cells from epithelia•Modulation of intracellular metabolism is involved in HFD-mediated suppression of EDAC•Chronic inflammation also negatively regulates the elimination of transformed cells•In HFD-fed mice, aspirin promotes the elimination of transformed cells from epithelia Sasaki et al. demonstrate using a cell competition mouse model that high-fat diet feeding substantially attenuates the frequency of apical elimination of RasV12-transformed cells from intestinal and pancreatic epithelia. These results indicate that obesity can profoundly influence competitive interaction between normal and transformed cells at the initial stage of carcinogenesis.