Western diet leads to aging-related tumorigenesis via activation of the inflammatory, UPR, and EMT pathways

Cell Death Dis. 2021 Jun 23;12(7):643. doi: 10.1038/s41419-021-03929-9.

Abstract

Among the principal causative factors for the development of complications related to aging is a diet rich in fats and sugars, also known as the Western diet. This diet advocates numerous changes that might increase the susceptibility to initiate cancer and/or to create a tissue microenvironment more conducive to the growth of malignant cells, thus favoring the progression of cancer and metastasis. Hypercaloric diets in general lead to oxidative stress generating reactive oxygen species and induce endoplasmic reticulum stress. Our results demonstrate that mice bearing tumors fed with a Western diet presented bigger tumor mass with increased insulin sensitivity in these tissues. Several markers of insulin signaling, such as AKT phosphorylation and mTOR pathway, are promoted in tumors of Western diet-fed animals. This process is associated with increased macrophage infiltration, activation of unfolded protein response pathway, and initiation of epithelial-mesenchymal transition (EMT) process in these tumor tissues. Summing up, we propose that the Western diet accelerates the aging-related processes favoring tumor development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Diet, High-Fat / adverse effects*
  • Diet, Western / adverse effects*
  • Epithelial-Mesenchymal Transition* / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic
  • Inflammation Mediators / metabolism*
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Signal Transduction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism
  • Time Factors
  • Tumor Burden
  • Tumor Microenvironment
  • Unfolded Protein Response* / genetics

Substances

  • Inflammation Mediators
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase
  • Receptor, Insulin