Grant: CIHR Fellowship

Cancer cells have distinct metabolic features that allow them to achieve uncontrolled proliferation, survival, and long-term maintenance. Cancer cells are known to have increased consumption of glucose for fermentation, namely the Warburg effect, but other metabolic pathways altered in tumorigenesis are largely unexplored. This proposal is to investigate the functional relevance of one carbon metabolism, particularly methionine in tumor growth. The study will focus on the interactions among methionine metabolism, tumour growth and cancer epigenetics. The methylation status of histones and DNA referred to as epigenetics determines cell state through regulating gene expression. The epigenetics, coupled with genetic sequence, determines gene expression and function and further contributes to physiological phenotypes and pathological symptoms. Epigenetic modifications are deregulated in cancer, demonstrating global DNA hypomethylation, but paradoxically hypermethylation of certain specific genes that are likely to be tumor suppressors. Enzymes modulating epigenetics are currently targets of many drug development efforts. However, the relevance of metabolism to methylation is largely unexplored. Dietary methionine provides direct substrate for generating the universal methyl-donor S-adenosylmethionine that further mediates cellular methylation reactions. Recent studies show the beneficial effects of dietary methionine restriction on obesity and longevity, two phenotypes closely related to anti-tumorigenicity. Our prior studies have also linked alterations of methionine metabolism with changes of histone methylation. This proposal will follow up to explore the effects of methionine restriction on tumour growth and cancer epigenetics through methylation. The outcome will determine the potential of methionine restriction as a cancer therapy, and will possibly uncover a new role of methionine metabolism in epigenetics that will be targeted for cancer therapy.