B細胞特異的なグルコース炭素利用の転換は,B細胞悪性腫瘍におけるユニークな脆弱性を明らかにする

¹Department of Systems Biology, Beckman Research Institute, and City of Hope Comprehensive Cancer Center, Monrovia, CA 91016, USA.

|March 20, 2018

まとめ

セリン/スレオニンタンパク質フォスファタゼ2A (PP2A) は,B細胞腫瘍において,酸化還元ホメオスタシスのために,グルコースをペントース・フォスファート経路 (PPP) に再誘導することが重要である. PP2AとG6PDを阻害することは,B細胞悪性腫瘍の治療戦略を提供します.

科学分野:

腫瘍学
免疫学
代謝経路

背景:

B細胞の活性化と癌は代謝需要と酸化ストレスを増大させます
セリン/スレオニンタンパク質フォスファタゼ2A (PP2A) は腫瘍抑制剤として知られていますが,B細胞腫瘍におけるその役割は不可欠です.
B細胞は,PAX5とIKZF1による転写抑制により,構成的に低いペントースリン酸経路 (PPP) 活性を持っています.

研究の目的:

PP2AがB細胞代謝とリドックスホメオスタシスにおける役割を調査する.
治療的に標的となるB細胞の脆弱性を特定する.

主な方法:

B細胞腫瘍の遺伝子研究
グルコースの炭素利用経路の分析 (糖分解とPPP)
酸化ストレスと抗酸化保護機構の評価

主要な成果:

PP2AはB細胞腫瘍に不可欠であり,グルコース代謝をグリコロシスからPPPにリダイレクトします.
このリダイレクトは B細胞の酸化ストレス管理に役立ちます
B細胞特異的なPPP酵素の転写抑制は,B細胞悪性腫瘍で利用可能な脆弱性を生み出します.
PP2AとG6PDの抑制は治療的可能性を示しています.

結論:

ペントースリン酸経路 (PPP) は,B細胞悪性腫瘍のゲートキーパーとして作用する.
小分子によるPP2AとG6PDの標的化は,B細胞がんに対する有望な治療戦略です.

キーワード:

B細胞の悪性腫瘍 G6PD について PP2A についてグルコース代謝系統特有の脆弱性レドックスホメオスタシストランスクリプション抑制

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