Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors.
Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors.
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DOI：
10.1016/j.cellsig.2012.09.024
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发表时间：
2013-01
影响因子：
4.8
通讯作者：
Bianco C
中科院分区：
文献类型：
--
作者：
Nagaoka T;Karasawa H;Turbyville T;Rangel MC;Castro NP;Gonzales M;Baker A;Seno M;Lockett S;Greer YE;Rubin JS;Salomon DS;Bianco C
通过激活复杂的信号通路网络，Cripto-1参与多种细胞事件，包括细胞增殖、运动和血管生成。先前已经描述了Cripto-1和典型Wnt/β-catenin信号通路之间的串扰。事实上，在胚胎和结肠癌细胞中，Cripto-1是典型的Wnt/β-catenin信号通路的下游靶基因，并且已经在小鼠和人类的Cripto-1基因的启动子和第一内含子区发现了t细胞因子(Tcf)/淋巴细胞增强因子的结合位点。我们现在证明，Cripto-1通过与Wnt共受体低密度脂蛋白受体相关蛋白（LRP） 5和LRP6结合，通过典型的Wnt/β-catenin/Tcf途径调节信号，从而促进Wnt3a与LRP5和LRP6结合。Cripto-1通过细胞质稳定β-catenin和提高β-catenin/Tcf转录激活，在功能上增强Wnt3a信号传导。相反，Wnt3a进一步增加了Cripto-1对HC11小鼠乳腺上皮细胞在软琼脂中的迁移、侵袭和集落形成的刺激，表明Cripto-1和典型的Wnt/β-catenin信号共同调节乳腺上皮细胞的运动和体外转化。
Cripto-1 is implicated in multiple cellular events, including cell proliferation, motility and angiogenesis, through the activation of an intricate network of signaling pathways. A crosstalk between Cripto-1 and the canonical Wnt/β-catenin signaling pathway has been previously described. In fact, Cripto-1 is a downstream target gene of the canonical Wnt/β-catenin signaling pathway in the embryo and in colon cancer cells and T-cell factor (Tcf)/lymphoid enhancer factor binding sites have been identified in the promoter and the first intronic region of the mouse and human Cripto-1 genes. We now demonstrate that Cripto-1 modulates signaling through the canonical Wnt/β-catenin/Tcf pathway by binding to the Wnt co-receptors low-density lipoprotein receptor-related protein (LRP) 5 and LRP6, which facilitates Wnt3a binding to LRP5 and LRP6. Cripto-1 functionally enhances Wnt3a signaling through cytoplasmic stabilization of β-catenin and elevated β-catenin/Tcf transcriptional activation. Conversely, Wnt3a further increases Cripto-1 stimulation of migration, invasion and colony formation in soft agar of HC11 mouse mammary epithelial cells, indicating that Cripto-1 and the canonical Wnt/β-catenin signaling co-operate in regulating motility and in vitro transformation of mammary epithelial cells.
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影响因子：
5.3
作者：
Bianco, C;Adkins, HB;Salomon, DS
通讯作者：
Salomon, DS
影响因子：
64.5
作者：
Gong, YQ;Slee, RB;Warman, ML
通讯作者：
Warman, ML
DOI：
10.1016/s0022-2828(02)00313-9
发表时间：
2003-02-01
影响因子：
5
作者：
Chu, PJ;Best, PM
通讯作者：
Best, PM
DOI：
10.1016/j.bbrc.2007.01.143
发表时间：
2007-03-30
影响因子：
3.1
作者：
Hamada, Shin;Watanabe, Kazuhide;Salomon, David S.
通讯作者：
Salomon, David S.
影响因子：
64.8
作者：
Reya, T;Clevers, H
通讯作者：
Clevers, H