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

• DOI: 10.1016/j.celrep.2018.03.104
• Publication Date: 2018-04-25T08:07:27Z
• Authors: Ayana Sasaki; Takahiro Nagatake; Riku Egami; Guoqiang Gu; Ichigaku Takigawa; Wataru Ikeda; Tomoya Nakatani; Jun Kunisawa; Yasuyuki Fujita
• Keywords: 2. Zero hunger; 0301 basic medicine; QH301-705.5; 490; Epithelial Cells; Lipid Metabolism; Dietary Fats; Article; Immunity, Innate; Madin Darby Canine Kidney Cells; 3. Good health; Mice; 03 medical and health sciences; Cell Transformation, Neoplastic; Dogs; Animals; Obesity; Biology (General); Intestinal Mucosa; Pancreas

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.