Tumor suppressor p53 restricts Ras stimulation of RhoA and cancer cell motility
Tumor suppressor p53 restricts Ras stimulation of RhoA and cancer cell motility
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DOI：
10.1038/nsmb1208
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发表时间：
2007-03-01
影响因子：
16.8
通讯作者：
Land, Hartmut
中科院分区：
文献类型：
--
作者：
Xia, Mingxuan;Land, Hartmut
癌细胞表型的许多特征是多个致癌突变之间合作的结果。本研究表明，激活的Ras（V12）和p53功能的缺失可以协同促进细胞运动，这一特征与癌症向恶性发展密切相关。我们的分析表明，Ras（V12）和p53的缺失协同诱导RhoA活性，揭示了p53在肿瘤抑制中的未知作用。p53通过一个简单的信号通路阻止RhoA的激活，从而通过Ras（V12）诱导细胞运动，该信号通路整合了汇聚在RhoA上的多个输入。我们的数据表明，p53通过调节Ras信号的质量来抑制癌症向恶性肿瘤的进展。
Many features of the cancer cell phenotype emerge as a result of cooperation between multiple oncogenic mutations. Here we show that activated Ras(V12) and loss of p53 function can cooperate to promote cell motility, a feature closely associated with cancer progression to malignancy. Our analysis indicates that Ras(V12) and loss of p53 synergistically induce RhoA activity, revealing a previously unknown role for p53 in tumor suppression. p53 prevents activation of RhoA and thus induction of cell motility by Ras(V12) through a simple signaling circuit, which integrates multiple inputs that converge on RhoA. Our data suggest that p53 suppresses cancer progression to malignancy by modulating the quality of Ras signaling.