癌細胞生存におけるサイクリンD3- CDK6キナーズの代謝機能

Haizhen Wang^1,2, Brandon N Nicolay³, Joel M Chick⁴

¹Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

Nature

|June 14, 2017

まとめ

サイクリンD3- CDK6キナーゼは,ガンの細胞の代謝をグリコリシスを再誘導することによって調節する. この複合体を抑制すると抗酸化物質が枯渇し反応性酸素種が増加し癌細胞が死亡します

科学分野:

腫瘍学
分子生物学
癌代謝

背景:

D型サイクリンとサイクリン依存キナーゼ (CDK) 4/6は細胞増殖に不可欠である.
CDK4/ 6阻害剤は,がん臨床試験において有望であることが示されています.

研究の目的:

癌細胞の代謝におけるサイクリンD3-CDK6の役割とその治療的影響を調査する.

主な方法:

ヒトの癌細胞とマウスの患者からの異種移植を用いた.
糖分解酵素と代謝経路に対するサイクリンD3-CDK6の効果を分析した.

主要な成果:

サイクリンD3-CDK6は,6-フォスフォフルトキナーゼとピルベートキナーゼM2をリン酸化し,抑制する.
これは,中間物質をペントースリン酸 (PPP) とセリン経路に誘導します.
サイクリンD3- CDK6の抑制はNADPHとグルタチオンを枯渇させ,反応性酸素種を増やし,アポトーシスを誘発する.

結論:

細胞サイクルと代謝を結びつけ,オンコタンパク質として作用する.
サイクリンD3- CDK6レベルを測定することで,CDK4/ 6抑制療法に反応する腫瘍を特定することができる.

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