突变p53通过促进整体蛋白循环利用来驱动入侵
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
概括
突变的p53蛋白质通过增强细胞信号通路来驱动癌症的入侵和转移. 向整合素和EGF受体可能提供新的癌症疗法.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- p53是一种关键的瘤抑制蛋白质,在癌症中经常因TP53基因的错误突变而失活.
- 突变的p53蛋白不仅丧失了瘤抑制功能,而且还获得了前转移性活动,促进了癌症的进展.
研究的目的:
- 研究突变p53促进癌细胞入侵和转移的机制.
- 确定关键的信号通路和分子参与突变p53驱动的瘤发生的参与者.
主要方法:
- 在突变p53.3存在的情况下分析细胞入侵,迁移和转移行为.
- 研究整合素和表皮生长因子受体 (EGFR) 的贩运和信号通路.
- 评估拉布结合蛋白 (RCP) 和TAp63在突变的p53功能中的作用.
主要成果:
- 突变的p53表达增强了细胞入侵,破坏了迁移的方向性,并促进了转移性行为.
- 这些效应是由增加的整体蛋白和EGFR贩运的介导,依赖于RCP,导致构成性EGFR/整体蛋白信号传递.
- 突变的p53通过TAp63抑制促进入侵;同时失去p53和TAp63模仿突变的p53表型.
结论:
- 突变p53通过重编程细胞信号和贩运通路,积极推动癌症的进展.
- 向α5/β1-整蛋白和/或EGFR代表了对表达突变p53.3的癌症的潜在治疗策略.
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