Japanese Society of Pathology Academic Research Award (Professor Kenji Oshima, Head of Department of Molecular Pathology)

Japanese Society of Pathology

Elucidation of the functions of metabolic enzymes that contribute to tumor progression

The elucidation of specific metabolic changes in cancer cells and the development of therapeutic approaches targeting these changes have been conducted since the early 1900s, and are one of the oldest cancer research fields. In recent years, with the development of technologies such as metabolome analysis, many metabolic dynamics specific to cancer cells have been revealed, and more specific cancer metabolic targeting therapeutic approaches are being developed. In this historical background, we have been conducting research to elucidate the functions of metabolic enzymes that contribute to cancer progression and to target them for treatment, based on the observation of the expression distribution of metabolic enzymes in human cancer tissues. Specifically, we have shown that reduced expression of argininosuccinate synthase 1, a rate-limiting enzyme in arginine synthesis, promotes tumor invasion by activating the mTORC1 signaling pathway in endometrioid cancer. We also showed that adenylosuccinate lyase, a purine synthesis enzyme, contributes to the malignancy of endometrioid cancer. We also showed that serine racemase, which racemises serine, produces pyruvate from serine, which contributes to the proliferation and chemotherapy resistance of colorectal cancer. Furthermore, we found that mitochondria maintain acetylated histone H3K27ac in colorectal cancer.