Scientists have studied many foods, nutrients, vitamins, and various types of diets for their links to cancer. Diets high in processed meat or saturated fats, for example, have been associated with increased risk for many types of cancer, while increased consumption of non-starchy vegetables, whole fruits, and fiber may lower cancer risk. As the National Cancer Institute points out, however, these studies only show that diet is associated with a change in cancer risk, not that any specific food or nutrient is directly responsible for that change.
Metabolomics is the field of biomedical research that studies metabolites produced by cells, including amino acids, lipids, carbohydrates, and more. Over the past several decades, researchers at the University of Chicago and elsewhere have begun to grasp how much characterizing metabolites and measuring their levels can tell us about how biological systems respond to genetic differences, environment, or disease, including cancer. Many of these metabolites originally come from diet—they are the downstream byproducts of the foods we eat as our cells consume and process them for all sorts of activities.
Jing Chen, PhD, the Janet Davison Rowley Distinguished Service Professor of Medicine at the University of Chicago, focuses on metabolomics in the context of cancer. Cancer cells produce and consume metabolites just like any other cells, but often in strange ways because they need increased energy to grow quickly. For example, normal cells use oxygen to turn food into energy through a process called oxidative phosphorylation. But cancer cells prefer to fuel their growth through glycolysis, a process that involves consuming and breaking down glucose for energy. This phenomenon, called “the Warburg effect,” is involved in virtually all cancers, so unraveling its mechanisms could have broad implications for understanding the links between metabolic processes and cancer.
At that level, Chen says it doesn’t matter where the nutrient or dietary substance came from, because understanding the role of different molecules at a basic level will give them clues how to intervene or develop therapies down the road.
“If there is a dietary substance or supplement, you don't need to care about the upstream diet or where it is from yet,” he said. “Instead, we can look at the molecular and signaling level to understand how it influences cancer development, initiation, progression and response to the therapy.” Indeed, Chen’s lab previously reported that both acetoacetate, a ketone body derived from dietary fat, and chondroitin sulfate, a widely used dietary supplement, promote tumor growth potential of melanoma cells expressing one common genetic mutation called BRAF V600E.
In a new study published recently in Molecular Cell, Chen and his team took this approach further to study an enzyme called PLA2G7. Normally, this is a protein that immune cells secrete to promote inflammation. But when Chen’s team screened melanoma cancer cells with various genetic mutations, they saw that some of them retain PLA2G7 inside the cells instead. PLA2G7 produces a byproduct called Lyso-PAF, which was thought to be a biologically inactive metabolite outside of the cells. When it’s retained, however, it plays a role in cell proliferation and tumor growth of melanoma cells expressing an alternative genetic mutation called NRAS, which is found in 15-20% of patients, but not in melanoma cells expressing BRAF V600E.
