脳腫瘍のメゼンキマ変換のための転写ネットワーク

Maria Stella Carro¹, Wei Keat Lim, Mariano Javier Alvarez

¹Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.

Nature

|December 25, 2009

まとめ

2つの転写因子,C/EBPbetaとSTAT3は,悪性結晶腫におけるメゼンキマの変異を駆動する. それらの活性化は,この攻撃的な腫瘍フェノタイプを起動し,維持し,潜在的な治療標的を提供します.

科学分野:

システム生物学システム生物学
がん研究がん研究
分子腫瘍学は分子腫瘍学である.

背景:

悪性膠原腫の攻撃性は,メゼンキマ現象型と関連しています.
このフェノタイプを駆動する規制ネットワークは,ほとんど不明です.
これらのネットワークを理解することは,ターゲティングセラピーの開発に不可欠です.

研究の目的:

悪性膠原腫におけるメゼンキマ遺伝子発現に責任を負う転写レギュレータを特定する.
膠原腫の発達と進行におけるこれらのレギュレータの役割を明らかにする.

主な方法:

グリオマ特有の規制ネットワークのリバースエンジニアリング.
トランスクリプションモジュールの公正な尋問.
転写因子発現 (共発現および除去) の実験操作.

主要な成果:

メゼンキマ遺伝子を活性化する特定の転写モジュールが特定されました.
C/EBPbetaとSTAT3は,メゼンキマ変異の重要なシナギスティックレギュレータであることが明らかになった.
神経幹細胞におけるC/EBPβとSTAT3誘発メゼンキマ系の共表現.
C/EBPβとSTAT3の除去により,髄膜細胞のシグネチャーとグリオマ細胞の攻撃性が低下した.
高C/EBPβとSTAT3発現は,メゼンキマの分化とヒト膠原腫の不良予後と相関する.

結論:

C/EBPbetaとSTAT3によって駆動される小さな調節モジュールは,癌細胞におけるメゼンキマ現象型の開始と維持に必要で十分である.
これらの発見は,C/EBPbetaとSTAT3をグリオマの攻撃性および潜在的な治療目標の重要な要因として強調しています.

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