Function of D-glutamate cyclase in colorectal cancer metabolism

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16220
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Osaka University
• Principal Investigator: Ohshima Kenji 大阪大学, 医学系研究科, 助教 (40817152)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 腫瘍代謝 / 大腸がん / ミトコンドリア / C14orf159

Outline of Final Research Achievements

Reprogramming of metabolism, including amino acid metabolism, is a hallmark of cancer, and it　supports their growth and metastasis. Most of the amino acids which consist of the human body are L-amino acids. However, human beings possess several D-amino acid metabolising enzymes, whose functions have not been well elucidated in cancer. In this study, we found that C14orf159, which is involved in D-glutamic acid metabolism, suppressed the proliferative, invasive and metastatic potential of human colorectal cancer. As a mechanism, we showed that C14orf159 suppresses the gene expression of MMP and Wnt family involved in the metastasis of colorectal cancer, and found that the mitochondrial membrane potential maintained by C14orf159 might be involved in the regulation of these gene expression.

Free Research Field

実験病理　人体病理　腫瘍代謝

Academic Significance and Societal Importance of the Research Achievements

がん細胞がL-アミノ酸代謝を改変していることは広く知られており多くの研究がなされている。しかし、がん細胞におけるD-アミノ酸代謝酵素の機能は、申請者らがこれまでの研究で示した大腸がんにおけるSerine racemaseの機能以外は明らかになっていなかった。本研究は、もう一つのD-アミノ酸代謝酵素であるC14orf159の大腸がんにおける機能を明らかにした。これらは、これまで未知であった「D-アミノ酸代謝酵素群」のがんにおける機能を明らかにするものであり学術的意義を有している。