Role of creatine cycle in cancer cachexia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19915
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Nara Medical University
• Principal Investigator: Goto Kei 奈良県立医科大学, 医学部, 研究員 (10469554)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: クレアチン・サイクル / CKB / mtCK / がん性悪液質 / がん性サルコペニア

Outline of Final Research Achievements

The creatine cycle is a pathway in which ATP produced in mitochondria is transferred to the cytoplasm in the form of phosphocreatine by mtCK in mitochondria and CKB in the cytoplasm. Then the creatine cycle is regarded as a third energy metabolism pathway. Inhibition of CKs with DNFB in colon cancer cells reduced tumor growth and stemness, and further inhibited the phosphorylation signaling pathways. In skeletal muscle cells, mtCK and CKB are involved in phosphorylation of p38, which activates skeletal muscle differentiation signaling. Induction of CKB expression restored cachexia-induced skeletal muscle maturation defects.

Free Research Field

リハビリテーション医学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、クレアチン・サイクルが骨格筋分化と成熟に重要な役割を果たしていることが明らかになった。癌においてはクレアチン・サイクルの抑制は癌を抑制するが、骨格筋においても筋成熟度の低下を招く。しかし、クレアチン・サイクルの活性化は悪液質による骨格筋障害を改善する。これらの結果から、クレアチン・サイクルの骨格筋選択的な活性化により、がん性サルコペニアの改善をもたらすことが可能であり、重要な分子標的と考えられた。