ミュータントのp53は,インテグリンリサイクルを促進することによって,侵入を推進しています
Patricia A J Muller1, Patrick T Caswell, Brendan Doyle
1The Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
Cell
|January 13, 2010
まとめ
変異したp53タンパク質は,細胞シグナル伝達経路を強化することによって,がんの侵入と転移を駆動する. インテグリンとEGF受容体へのターゲティングは,新しいがん治療法を提供することができる.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- p53は重要な腫瘍抑制タンパク質で,TP53遺伝子のミスセンスの変異によってがんでは頻繁に無活性化されます.
- 変異したp53タンパク質は,腫瘍抑制機能を失うだけでなく,転移前活動も獲得し,がんの進行に貢献します.
研究 の 目的:
- 変異性p53ががん細胞の侵入と転移を促進するメカニズムを調査する.
- 重要な信号伝達経路と,変異性p53駆動型腫瘍形成に関与する分子プレーヤーを特定する.
主な方法:
- ミュータントp53.3の存在下における細胞侵入,移動,転移行動の分析
- インテグリンと表皮成長因子受容体 (EGFR) の密輸とシグナル伝達経路の調査.
- 変異したp53の機能におけるラブ結合タンパク質 (RCP) とTAp63の役割の評価.
主要な成果:
- ミュータントのp53発現は細胞の侵入を強化し,移住の方向性を破壊し,転移行動を促進します.
- これらの効果は,RCPに依存するインテグリンとEGFRの密輸の増加によって媒介され,構成的なEGFR/インテグリンシグナリングにつながります.
- 変異性p53は,TAp63の阻害によって侵入を促進し,p53とTAp63の同時喪失は変異性p53の表型を模倣する.
結論:
- 変異したp53は,細胞シグナル伝達とトラフィックの経路を再プログラムすることによって,がんの進行を積極的に推進します.
- アルファ5/ベータ1-インテグリンおよび/またはEGFRをターゲットにすることは,p53.3変異体を発現するがんに対する潜在的な治療戦略です.
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