Tumor progression through epigenetics remodeling by RB-PGAM

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K14992
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: Kohno Susumu 金沢大学, がん進展制御研究所, 特任助教 (30625463)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: RB / PGAM / KDM5A / エピジェネティクス

Outline of Final Research Achievements

The metabolic intermediates produced in the glycolytic or TCA cycle are utilized in various pathways. We focused on the tumor suppressor gene RB, which is frequently inactivated in the malignant progression of cancer, and found that the expression of glycolytic enzyme PGAM1 is regulated by RB. In this study, we focused on the metabolic changes caused by RB inactivation and analyzed the impact given by the metabolic alteration on epigenetics. As a result, RB regulates global methylation in gastric cancer via KDM5A, and it is revealed that various glycolytic enzymes are controlled by the RB-KDM5A axis. In addition, we found that PGAM contributes RB dependent cell differentiation in myogenesis of C2C12 and adipogenesis of 3T3L1.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

これまでに、何故がん細胞は、グルコースを積極的に利用するのか、その生理的意義と本質に迫ることができていない。本研究では、がん悪性進展課程におけるRBの不活性化に伴い、グルコースの利用が下がるという、従来の「がん特異的代謝」の概念とは逆の現象に着目し、エピジェネティクスの観点からがん代謝の理解を試みたものである。