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Cdc42 regulates anchorage-independent growth and is necessary for Ras transformation.

机译：Cdc42调节锚定非依赖性生长，并且是Ras转化所必需的。

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The Rho family members Cdc42, Rac, and Rho play a central role in the organization of the actin cytoskeleton and regulate transcription. Whereas Rac and Rho have been implicated in transformation by oncogenic Ras, the role of Cdc42 in this process remains unknown. In this study, we found that Rat1 fibroblasts expressing constitutively active V12-Cdc42 were anchorage independent and proliferated in nude mice but failed to show enhanced growth in low serum. Similar to V12-Rac1-expressing Rat1 fibroblasts, V12-Cdc42 lines displayed a high frequency of multinucleated cells. Interestingly, coexpression of dominant negative N17-Rac1 blocked the V12-Cdc42-induced multinucleated phenotype but not growth in soft agar, indicating that Cdc42 controls anchorage independence in a Rac-independent fashion. We also showed that dominant negative N17-Cdc42 inhibited Ras focus formation and anchorage-independent growth and caused reversion of the transformed morphology, indicating that Cdc42 is necessary for Ras transformation. N17-Cdc42 caused only partial inhibition of Ras-induced low-serum growth, however. In contrast, whereas N17-Rac1 also effectively inhibited Ras-induced anchorage independence, it did not revert the morphology of Ras-transformed cells. N17-Rac1 strongly inhibited low-serum growth of Ras-transformed cells, however. Together, these data provide a novel function for Cdc42 in cell proliferation and indicate that Cdc42 and Rac play distinct roles in growth control and Ras transformation.
机译：Rho家族成员Cdc42，Rac和Rho在肌动蛋白细胞骨架的组织和调节转录中起着核心作用。尽管Rac和Rho参与了致癌Ras的转化，但Cdc42在此过程中的作用仍然未知。在这项研究中，我们发现表达组成型活性V12-Cdc42的Rat1成纤维细胞不依赖锚定并在裸鼠中增殖，但在低血清中未显示出增强的生长。与表达V12-Rac1的Rat1成纤维细胞相似，V12-Cdc42系显示出高频率的多核细胞。有趣的是，显性阴性N17-Rac1的共表达阻断了V12-Cdc42诱导的多核表型，但在软琼脂中却没有生长，表明Cdc42以Rac独立的方式控制了锚定独立性。我们还显示，显性负性N17-Cdc42抑制Ras焦点形成和锚定非依赖性生长，并导致转化的形态发生逆转，表明Cdc42是Ras转化所必需的。 N17-Cdc42仅引起Ras诱导的低血清生长的部分抑制。相反，虽然N17-Rac1也有效抑制了Ras诱导的锚定独立性，但它没有还原Ras转化细胞的形态。但是，N17-Rac1强烈抑制了Ras转化细胞的低血清生长。总之，这些数据为Cdc42在细胞增殖中提供了一种新颖的功能，并表明Cdc42和Rac在生长控制和Ras转化中起着不同的作用。

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