Altered Glucose Metabolism in Cancer Metastasis and Drug Resistance

Glucose, one of the most important energy sources for living organisms, is first broken down through glycolysis then either undergoes oxidative phosphorylation in the mitochondrion or fermentation in the cytosol. Abnormal glucose metabolism was first discovered by Dr. Otto Warburg, i.e. cancer cells carry out irreversible fermentation of glucose in the presence of oxygen, which is also termed aerobic glycolysis. My studies focus on understanding altered glucose metabolism in cancer metastasis and drug resistance. We found that breast cancer brain metastasized cells developed enhanced oxidation of certain amino acids and gluconeogenic activity for survival and proliferation when glucose level is limited. We also found that drug-resistant colon cancer cells exhibited up-regulated aerobic glycolysis to meet the need of a higher amount of intracellular ATP to cope with chemotherapeutic stress. These results suggest alterations in glucose metabolism play critical roles in the development of cancer brain metastasis and drug resistance. The molecular mechanisms identified by this study may serve as potential therapeutic targets for cancer treatment.