Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells.
Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells.
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DOI：
10.1038/ncomms3610
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发表时间：
2013
影响因子：
16.6
通讯作者：
Boutros, Michael
中科院分区：
文献类型：
--
作者：
Voloshanenko, Oksana;Erdmann, Gerrit;Dubash, Taronish D.;Augustin, Iris;Metzig, Marie;Moffa, Giusi;Hundsrucker, Christian;Kerr, Grainne;Sandmann, Thomas;Anchang, Benedikt;Demir, Kubilay;Boehm, Christina;Leible, Svenja;Ball, Claudia R.;Glimm, Hanno;Spang, Rainer;Boutros, Michael
Wnt/β-catenin通路的异常调控在结直肠癌的发生发展过程中起着重要作用，90%以上的散发性结肠癌患者存在APC或β-catenin基因突变。然而，这些突变是否足以激活该途径或需要额外的上游信号仍然是一个争议点。在这里，我们显示结直肠肿瘤表达高水平的WNT3和EVI/WLS/GPR177。我们发现，在结肠癌细胞中，即使在APC或β-连环蛋白突变的情况下，下游信号仍然对Wnt配体和受体近端信号做出反应。此外，我们还证明截短的蛋白结合了β-连环蛋白和破坏复合体的关键成分。这些结果表明，具有APC或β-连环蛋白突变的细胞依赖WNT配体及其分泌的足够水平的β-连环蛋白信号，这可能为通过EVI/WLS靶向WNT分泌而进行治疗干预开辟新的途径。Wnt信号通路中的激活突变与结肠癌有关。在这里，作者表明携带APC和β-连环蛋白突变的肿瘤细胞仍然受到Wnt配体的调节，这表明Wnt的分泌和受体信号传递对于控制下游信号仍然很重要。
Aberrant regulation of the Wnt/β-catenin pathway has an important role during the onset and progression of colorectal cancer, with over 90% of cases of sporadic colon cancer featuring mutations in APC or β-catenin. However, it has remained a point of controversy whether these mutations are sufficient to activate the pathway or require additional upstream signals. Here we show that colorectal tumours express elevated levels of Wnt3 and Evi/Wls/GPR177. We found that in colon cancer cells, even in the presence of mutations in APC or β-catenin, downstream signalling remains responsive to Wnt ligands and receptor proximal signalling. Furthermore, we demonstrate that truncated APC proteins bind β-catenin and key components of the destruction complex. These results indicate that cells with mutations in APC or β-catenin depend on Wnt ligands and their secretion for a sufficient level of β-catenin signalling, which potentially opens new avenues for therapeutic interventions by targeting Wnt secretion via Evi/Wls. Activating mutations in the Wnt signalling pathway are associated with colon cancer. Here the authors show that tumour cells carrying mutations in APC and β-catenin are still regulated by Wnt ligands, suggesting that Wnt secretion and receptor signalling remains important to control downstream signalling.
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各种人类截短的腺瘤性息肉病大肠杆菌同工型在控制β-蛋白 - - - - - - 钙蛋白活性和细胞增殖中）的共同作用。
影响因子：
3.7
作者：
Chandra SH;Wacker I;Appelt UK;Behrens J;Schneikert J
通讯作者：
Schneikert J
影响因子：
3.7
作者：
Fuerer C;Nusse R
通讯作者：
Nusse R
影响因子：
6
作者：
Brabletz, T;Herrmann, K;Kirchner, T
通讯作者：
Kirchner, T
影响因子：
29.4
作者：
Farin, Henner F.;Van Es, Johan H.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
3.5
作者：
Albuquerque, C;Breukel, C;Smits, R
通讯作者：
Smits, R