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

Cell Rep. 2018 Apr 24;23(4):974-982. doi: 10.1016/j.celrep.2018.03.104.

Abstract

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.

Keywords: Aspirin; EDAC; RasV12; apical extrusion; cancer prevention; cell competition; chronic inflammation; lipid metabolism; obesity; pancrease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology*
  • Cell Transformation, Neoplastic / pathology
  • Dietary Fats / adverse effects*
  • Dietary Fats / pharmacology
  • Dogs
  • Epithelial Cells / immunology*
  • Epithelial Cells / pathology
  • Immunity, Innate / drug effects*
  • Immunity, Innate / genetics
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Lipid Metabolism / immunology
  • Madin Darby Canine Kidney Cells
  • Mice
  • Obesity / chemically induced
  • Obesity / genetics
  • Obesity / immunology*
  • Obesity / pathology
  • Pancreas / immunology*
  • Pancreas / pathology

Substances

  • Dietary Fats