The Molecular Link from Diet to Cancer Cell Metabolism

Abstract

Malignant cells remodel their metabolism to meet the demands of uncontrolled cell proliferation. These demands lead to differential requirements in energy, biosynthetic precursors, and signaling intermediates. Both genetic programs arising from oncogenic events and transcriptional programs and epigenomic events are important in providing the necessary metabolic network activity. Accumulating evidence has established that environmental factors play a major role in shaping cancer cell metabolism. For metabolism, diet and nutrition are the major environmental aspects and have emerged as key components in determining cancer cell metabolism. In this review, we discuss these emerging concepts in cancer metabolism and how diet and nutrition influence cancer cell metabolism.

Conflict of interest statement

Declaration of Interests J.W.L. advises Nanocare Technologies, Raphael Pharmaceuticals, and Restoration Foodworks.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1:

Dietary compositions affect circulating metabolic factors and nutrient availability which, in turn, are thought to have effects on tumor cell metabolism. Dietary timing as well as caloric compositions are known to affect endocrine secretions of insulin which thereby affect cellular uptake of glucose. Limitations of glucose and an abundance of ketone bodies during the ketosis induced by the ketogenic diet has been linked to reduced glycolysis and enhanced oxidative processing. These suggest that, while these mechanisms are not well understood, diets may have important roles in driving cancer cell metabolism.

Figure 2:

Circulating amino acids are metabolized in cancer cells to provide unique biosynthetic and energetic requirements of the tumor. Abbreviations: MTAP (S-methyl-5’-thioadenosine phosphorylase), MAT2A (Methionine Adenosyltransferase 2A), MTA (5’-methylthioadenosine), THF (tetrahydrofolate), BCAT1 (Branched chain amino acid transaminase 1), FTCD (Formimidoyltransferase cyclodeaminase)