Cdc42 in oncogenic transformation, invasion, and tumorigenesis.
Cdc42 in oncogenic transformation, invasion, and tumorigenesis.
复制标题
DOI：
10.1016/j.cellsig.2011.04.001
复制
发表时间：
2011-09
影响因子：
4.8
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Stengel K;Zheng Y
GTP酶的Rho家族代表了一类Ras相关的信号分子，通常在癌症中失调。Rho GTP酶响应于细胞外刺激物如有丝分裂原和细胞外基质，从GDP结合的非活性状态转换为GTP结合的活性状态。此外，Rho GT3信号传导可以响应于细胞内在因素而改变，例如致癌或肿瘤抑制信号传导的变化。在其活性形式中，这些蛋白质结合许多效应分子，激活信号传导级联，其调节多种细胞过程，包括细胞骨架重组、细胞周期进程、细胞极性和转录。在这里，我们专注于Rho家族成员Cdc42，它在许多人类癌症中过表达。与促进肿瘤发生的作用一致，Cdc42和鸟嘌呤核苷酸交换因子中的激活突变正在转化，而Cdc42活性的抑制可以在癌蛋白激活或肿瘤抑制功能丧失后影响细胞转化。此外，Cdc42活性与表征肿瘤转移的侵袭性表型有关，进一步表明Cdc42可能是治疗干预的有用靶点。然而，最近在小鼠中的几项研究揭示了Cdc42在几种组织类型中可能涉及细胞极性维持的假定肿瘤抑制功能，这表明Cdc42在癌症发展中的作用是复杂的，并且可能是细胞类型特异性的。
The Rho family of GTPases represents a class of Ras-related signaling molecules often deregulated in cancer. Rho GTPases switch from a GDP-bound, inactive state to a GTP-bound, active state in response to extracellular stimuli such as mitogens and extracellular matrix. In addition, Rho GTPase signaling can be altered in response to cell intrinsic factors such as changes in oncogenic or tumor suppressor signaling. In their active form, these proteins bind to a number of effector molecules, activating signaling cascades which regulate a variety of cellular processes including cytoskeletal reorganization, cell cycle progression, cell polarity and transcription. Here, we focus on one Rho family member, Cdc42, which is overexpressed in a number of human cancers. Consistent with a role in the promotion of tumorigenesis, activating mutations in Cdc42 and guanine nucleotide exchange factors are transforming, while inhibition of Cdc42 activity can impinge on cellular transformation following the activation of oncoproteins or loss of tumor suppressor function. Furthermore, Cdc42 activity has been implicated in the invasive phenotype which characterizes tumor metastasis, further suggesting that Cdc42 may be a useful target for therapeutic intervention. However, several recent studies in mice have unveiled a putative tumor suppressor function of Cdc42 in several tissue types which may involve cell polarity maintenance, suggesting that the role of Cdc42 in cancer development is complex and may be cell type specific.
登录
查看更多内容
影响因子：
4.8
作者：
Debidda, M;Wang, L;Zheng, Y
通讯作者：
Zheng, Y
影响因子：
8
作者：
Cheung, L. W. T.;Leung, P. C. K.;Wong, A. S. T.
通讯作者：
Wong, A. S. T.
DOI：
10.1083/jcb.200403043
发表时间：
2004-12-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chu YS;Thomas WA;Eder O;Pincet F;Perez E;Thiery JP;Dufour S
通讯作者：
Dufour S
影响因子：
3.8
作者：
Appledorn DM;Dao KH;O'Reilly S;Maher VM;McCormick JJ
通讯作者：
McCormick JJ
影响因子：
4
作者：
Fisher, Kevin E.;Sacharidou, Anastasia;Davis, George E.
通讯作者：
Davis, George E.