Rac的激活和非激活控制瘤细胞运动的可塑性
Victoria Sanz-Moreno1, Gilles Gadea, Jessica Ahn
1Institute of Cancer Research, Cancer Research UK Centre for Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, UK.
Cell
|November 6, 2008
概括
瘤细胞通过调节Rho和Rac信号通路,在介质细胞和蜂体运动之间切换. 这项研究确定了控制这些关键细胞迁移模式的关键分子参与者.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 分子生物学分子生物学
背景情况:
- 瘤细胞表现出不同的迁移方式:介质细胞和蜂细胞.
- 介酶体运动涉及延长细胞,蛋白质分解和Rac信号传递.
- 氨基球体运动的特点是圆形的细胞,Rho-酶信号传递,以及高的actomyosin收缩性.
研究的目的:
- 阐明调节介质细胞和菌体瘤细胞运动之间的相互转换的分子机制.
- 确定关键信号通路和调节这些独特细胞迁移模式的蛋白质.
主要方法:
- 研究了GTPases Rac和Rho-kinase信号传递在调节细胞形态和运动中的作用.
- 利用涉及NEDD9,DOCK3,WAVE2和ARHGAP22的分子复合体来研究Rac和Rho的活动.
- 分析了控制瘤细胞迁移的Rho和Rac信号通路之间的相互作用.
主要成果:
- 介酶体运动是由Rac通过NEDD9-DOCK3复合体的激活驱动的,NEDD9-DOCK3复合体通过WAVE2.2发出信号.
- Rac的激活抑制了actomyosin的收缩性,抑制了阿米体的运动.
- 罗酶信号激活ARHGAP22,一个Rac GAP,它通过非活化Rac.抑制介酶运动.
结论:
- 瘤细胞迁移模式是由Rho和Rac信号之间的动态相互作用决定的.
- 了解这些切换机制,可以了解黑色素瘤转移和潜在的治疗点.
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