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

Area of Science:

• Oncology
• Cell Biology
• Metabolism

Background:

• Emerging transformed cells are typically eliminated by normal epithelial cells through a process called epithelial defense against cancer (EDAC).
• The mechanisms by which EDAC is compromised during carcinogenesis are not fully understood.

Purpose of the Study:

• To investigate how high-fat diet (HFD) affects EDAC in epithelial tissues.
• To explore the role of lipid metabolism and inflammation in HFD-induced changes to EDAC.
• To evaluate the potential of aspirin in restoring EDAC in HFD-fed mice.

Main Methods:

• Utilized a cell competition mouse model to study transformed cells in intestinal and pancreatic epithelia.
• Administered HFD to mice to induce obesity and associated metabolic changes.
• Assessed the frequency of transformed cell elimination under HFD conditions.
• Investigated the impact of aspirin treatment on transformed cell eradication.

Main Results:

• HFD feeding significantly reduced the elimination of RasV12-transformed cells from intestinal and pancreatic epithelia.
• This attenuation of EDAC was linked to alterations in lipid metabolism and the induction of chronic inflammation.
• Aspirin treatment markedly enhanced the clearance of transformed cells in HFD-fed mice.

Conclusions:

• Obesity, induced by HFD, profoundly impairs epithelial defense against cancer by disrupting normal cell competition.
• Lipid metabolism and chronic inflammation are key mediators of HFD's effect on EDAC.
• Aspirin demonstrates potential as an intervention to bolster cancer prevention in the context of obesity.