がん変異と標的薬は,Ras-Erk経路によるダイナミック信号エンコーディングを妨げる
L J Bugaj1, A J Sabnis2,3, A Mitchell1
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|September 1, 2018
まとめ
ラス・エルク経路のシグナルダイナミクスの変化は 細胞増殖を促すだけでなく オプトジェネティックプロファイリングは,突然変異と阻害物質が 時間の情報伝送を歪め,細胞の運命決定に影響を与え,癌に潜在的に寄与することを明らかにします.
科学分野:
- セルラー信号
- 分子生物学
- 癌の研究
背景:
- ラス・エルク経路は 細胞表面から核に信号を送信します
- 細胞の運命を決定するために,ERKの活動期間と頻度を含むシグナルダイナミクスは極めて重要です.
- 正確な時間情報伝達は 適切なセルラー意思決定に不可欠です
研究 の 目的:
- 腫瘍性B-Raf変異とB-Raf阻害剤がRas-Erk信号のダイナミックな伝達にどのように影響するかを調査する.
- 信号伝送の障害が 細胞増殖と運命決定の 変化につながることを理解する
- 信号経路の機能不全を解剖する際の光遺傳学的プロファイルの有用性を実証する.
主な方法:
- Ras-Erk経路の活動を正確に制御し,測定するために光遺伝的プロファイリングを使用しました.
- 時間の情報伝送を評価するために入力Rasの短いパルスを適用します.
- 下流転写変化と細胞運命を分析した.
主要な成果:
- 腫瘍性B-Raf変異とB-Raf阻害剤の両方が,Ras活動の時間的な伝播を歪めた.
- 短い入力パルスは異常な長さのErk活動出力に変換されました.
- これらのダイナミックなシグナル伝達の変化は 異常な細胞増殖を促し 細胞の運命を変化させました
結論:
- 機能不全のダイナミック信号伝達は 細胞増殖を促し 癌に寄与するだけではありません
- オプトジェネティックプロファイリングは 病気のシグナリング機能障害のメカニズムを 分解する強力なツールです
- 信号のダイナミクスを理解することは,細胞運命を決定し,病気の病原性を理解するために重要です.
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