Wnt signaling stimulates transcriptional outcome of the Hedgehog pathway by stabilizing GLI1 mRNA.
Wnt signaling stimulates transcriptional outcome of the Hedgehog pathway by stabilizing GLI1 mRNA.
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DOI：
10.1158/0008-5472.can-09-1500
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发表时间：
2009-11-15
期刊：
影响因子：
11.2
通讯作者：
Spiegelman VS
中科院分区：
文献类型：
--
作者：
Noubissi FK;Goswami S;Sanek NA;Kawakami K;Minamoto T;Moser A;Grinblat Y;Spiegelman VS
Wnt 和 Hedgehog 信号通路在胚胎发生、干细胞维持和肿瘤发生中发挥着核心作用。然而，这两种途径相互作用的机制尚不清楚。在这里，我们发现了 Wnt 信号通路刺激 Hedgehog 信号转录输出的新机制。 Wnt/β-连环蛋白信号传导诱导 RNA 结合蛋白 CRD-BP 的表达，CRD-BP 反过来结合并稳定 GLI1 mRNA，导致 GLI1 表达和转录活性升高。新描述的 GLI1 调节模式似乎对 Wnt 的多种功能很重要，包括结直肠癌细胞的存活和增殖。
Wnt and Hedgehog signaling pathways play central roles in embryogenesis, stem cell maintenance, and tumorigenesis. However, mechanisms by which these two pathways interact are not well-understood. Here, we identified a novel mechanism by which Wnt signaling pathway stimulates the transcriptional output of Hedgehog signaling. Wnt/β-catenin signaling induces expression of an RNA-binding protein, CRD-BP, which, in turn, binds and stabilizes GLI1 mRNA, causing an elevation of GLI1 expression and transcriptional activity. The newly described mode of regulation of GLI1 appears to be important to several functions of Wnt, including survival and proliferation of colorectal cancer cells.