特別講演
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1A-PL-1440 PDF
次世代プロテオミクスが拓く医学生物学の新地平：100年来のがん代謝の謎に迫る
Although glucose metabolism is remodeled in cancer (Warburg effect), the global pattern of cancer-specific metabolic changes has remained unclear. Comprehensive measurement of metabolic enzymes by the next-generation proteomics termed “iMPAQT” revealed that the metabolic flux of not only carbon but also nitrogen is altered during malignant progression of cancer. The fate of glutamine, a major source of nitrogen, is shifted from glutaminolysis to nucleotide biosynthesis, with this shift being controlled predominantly by GLS1 and PPAT in the respective pathways. The PPAT/GLS1 ratio is increased in many types of cancer, and interventions to reduce this ratio suppressed tumor growth. A meta-analysis of ~11,000 cancer patients revealed that enzymes of the nucleotide biosynthesis pathway are the strongest indicators of cancer malignancy among all metabolic enzymes. This trend is most pronounced in neuroendocrine tumors including small cell lung cancer (SCLC). PPAT depletion suppresses the growth of SCLC lines. Our results suggest that a shift in glutamine fate is required for malignant progression of cancer and may prove to be as important as the carbon shift (Warburg effect). This nitrogen shift might thus be referred to as a “second” Warburg effect.