Metabolic regulation by RB tumor suppressor gene

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03576
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: Takahashi Chiaki 金沢大学, がん進展制御研究所, 教授 (50283619)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: がん / がん抑制遺伝子 / RB / 代謝 / がん代謝

Outline of Final Research Achievements

We conducted comprehensive search of the molecular basis of RB1 function in the context of various malignant progresses, and found that SREBP transcription factors and PGAM1 and 2 are important targets of RB1. Based on these findings, we proposed a concept that RB1 regulates undifferentiated behavior of cells by controlling the metabolism in addition to regulating the cell cycle and coordinating with tissue-specific transcription factors. By analyzing in detail the mechanism by which RB1 regulates metabolism and its physiological significance, we are clarifying the true nature of cancer metabolism as a target for cancer treatment. We also obtained POCs for some of the target genes of RB1 as therapeutic targets.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

RB1は、あらゆる細胞増殖シグナルが行き着き、これを細胞周期進行制御へと結びつけるアダプタ分子であり、RB1を含むRB
パスウェイはほぼ全てのがんの制御に関わる。この分子の新規の機能を発見し、これをがん治療に活用するための標的分子を多数同定した。RB1が糖代謝、脂質代謝、核酸代謝とあらゆる代謝経路を制御する事も解明した。RB1を細胞周期と代謝をリンクする分子として位置づけた。これらの知見は、代謝面からがんを攻略する治療戦略の開発に大いに貢献すると考える。