腫瘍のアセタート依存症

Sarah A Comerford¹, Zhiguang Huang², Xinlin Du²

¹Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Cell

|December 20, 2014

まとめ

酵素ACSS2 (アセチル-コア合成酵素2) は,アセチールを用いて腫瘍の成長を助ける. ACSS2を阻害すると,マウスの腫瘍サイズが著しく減少し,それが示唆された.

科学分野:

バイオケミストリーバイオケミストリー
メタボリック経路は
がん生物学がん生物学

背景:

アセチル-CoA (AcCoA) は細胞のエネルギー,成長,遺伝子調節に不可欠です.
高分糖分解または低酸素の腫瘍は,生存のためにAcCoAに依存しています.
ACSS2は,AcCoAの代謝における重要な酵素である.

研究の目的:

腫瘍代謝における核細胞塩酸アセチル-CoA合成酵素 (ACSS2) の役割を調査する.
ACSS2が癌の潜在的な治療標的であるかどうかを判断する.

主な方法:

ACSS2酵素が欠けているマウスを使用した.
腫瘍負荷は2つの肝細胞癌モデルで評価されました.
細胞のアセテート吸収と脂質とヒストンへの組み込みが測定されました.

主要な成果:

ACSS2が欠けているマウスは,腫瘍負荷の有意な減少を示した.
ACSS2の活動は,細胞のアセテート吸収の大部分を占めました.
ACSS2は,ヒト腫瘍の大部分で発現しています.

結論:

ACSS2は,アセテートを活用した腫瘍に対するAcCoAの重要な源である.
ACSS2は,幅広い腫瘍の標的となる代謝的脆弱性を表しています.
ACSS2をターゲットにすることで,がん治療の新たな治療戦略が提供される可能性があります.

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