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首页> 外文期刊>Cellular Signalling >Rho GTPase activity modulates Wnt3a/beta-catenin signaling
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Rho GTPase activity modulates Wnt3a/beta-catenin signaling

机译：Rho GTPase活性调节Wnt3a /β-catenin信号传导

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摘要

Wnt proteins constitute a family of secreted signaling molecules that regulate highly conserved pathways essential for development and, when aberrantly activated. drive oncogenesis in a number of human cancers. A key feature of the most widely studied Wnt signaling cascade is the stabilization of cytosolic beta-catenin, resulting in beta-catenin nuclear translocation and transcriptional activation of multiple target genes. In addition to this canonical, beta-catenin-dependent pathway, Wnt3A has also been shown to stimulate RhoA GTPase. While the importance of activated Rho to non-canonical Wnt signaling is well appreciated, the potential contribution of Wnt3A-stimulated RhoA to canonical beta-catenin-dependent transcription has not been examined and is the focus of this study. We find that activated Rho is required for Wnt3A-stimulated osteoblastic differentiation in C3H10T1/2 mesenchymal stem cells, a biological phenomenon mediated by stabilized beta-catenin. Using expression microarrays and real-time RT-PCR analysis, we show that Wnt3A-stimulated transcription of a subset of target genes is Rho-dependent, indicating that full induction of these Wnt targets requires both beta-catenin and Rho activation. Significantly, neither beta-catenin stabilization nor nuclear translocation stimulated by Wnt3A is affected by inhibition or activation of RhoA. These findings identify Rho activation as a critical element of the canonical Wnt3A-stimulated, beta-catenin-dependent transcriptional program.
机译：Wnt蛋白构成了分泌的信号分子分子家族，可调节高度保守的发育通路，并在异常激活时对其进行调节。在许多人类癌症中驱动肿瘤发生。研究最广泛的Wnt信号级联反应的关键特征是胞质β-catenin的稳定，导致β-catenin核易位和多个靶基因的转录激活。除了这种典型的，β-catenin依赖性途径外，Wnt3A还被证明可以刺激RhoA GTPase。尽管人们很清楚激活的Rho对非经典Wnt信号传导的重要性，但尚未研究Wnt3A刺激的RhoA对经典β-catenin依赖性转录的潜在贡献，并且是本研究的重点。我们发现活化的Rho是C3H10T1 / 2间充质干细胞中Wnt3A刺激的成骨细胞分化所必需的，这是由稳定的β-catenin介导的生物学现象。使用表达微阵列和实时RT-PCR分析，我们显示Wnt3A刺激的靶基因子集的转录是Rho依赖性的，表明这些Wnt靶标的完全诱导需要β-catenin和Rho激活。值得注意的是，Wnt3A刺激的β-catenin稳定或核易位均不受RhoA抑制或激活的影响。这些发现确定Rho激活是Wnt3A刺激，β-catenin依赖的转录程序的规范的关键因素。

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