Helicobacter pylori-induced activation of beta-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled.
Helicobacter pylori-induced activation of beta-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled.
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DOI：
10.1186/1476-4598-9-31
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发表时间：
2010-02-05
期刊：
影响因子：
37.3
通讯作者：
Naumann M
中科院分区：
文献类型：
--
作者：
Gnad T;Feoktistova M;Leverkus M;Lendeckel U;Naumann M
人类微生物病原体幽门螺杆菌存在于世界约50%的人口的胃中，是慢性胃炎、消化性溃疡的危险因素，在极少数情况下还会导致胃癌。由于参与细胞周期控制、分化、细胞迁移或干细胞控制的靶基因的调节，几乎在所有人类癌症疾病中都描述了Wnt/β-Catenin信号通路的变化。本研究旨在阐明幽门螺杆菌感染胃上皮细胞后早期WnT信号转导元件低密度脂蛋白受体相关蛋白6(LRP6)和脱发蛋白(DVL)在β-catenin激活中的作用。幽门螺杆菌感染NCI-N87细胞可诱导非细胞毒素相关基因A(CagA)或空泡毒素A(VacA)的Wnt/β-连环蛋白途径共受体LRP6的快速磷酸化。然而，缺乏功能性类型4分泌系统(T4SS)的细菌不能诱导LRP6磷酸化。此外，我们还鉴定了参与LRP6磷酸化的Dvl2和Dvl3家族的蛋白质。幽门螺杆菌诱导的β-连环蛋白的核积聚及其转录激活和Wnt靶基因的表达在缺乏LRP6、Dvl2或Dvl3的稳定敲除细胞系中显著减少。我们分析了幽门螺杆菌诱导的Wnt信号因子的激活，并首次证明了规范的Wnt信号蛋白LRP6、Dvl2和Dvl3参与了β-catenin的调节。
The human microbial pathogen Helicobacter pylori resides in the stomach of about fifty percent of the world's population and represents a risk factor for chronic gastritis, peptic ulcers and, in rare cases, gastric cancer. Alterations of the Wnt/β-catenin signaling pathway have been described in almost every human cancer disease, due to the regulation of target genes being involved in cell cycle control, differentiation, cell migration or stem cell control. Our study aimed to elucidate the role of proximal Wnt signaling components low density lipoprotein receptor-related protein 6 (LRP6) and Dishevelled (Dvl) in the activation of β-catenin early after infection of gastric epithelial cells with H. pylori. Infection of gastric epithelial NCI-N87 cells with H. pylori induces rapid phosphorylation of the Wnt/β-catenin pathway co-receptor LRP6 independent of the cytotoxin-associated gene A (CagA) or vacuolating cytotoxin A (VacA). However, bacteria lacking a functional type 4 secretion system (T4SS) failed to induce LRP6 phosphorylation. Further, we identified proteins of the Dvl family, namely Dvl2 and Dvl3, which are involved in LRP6 phosphorylation. H. pylori-induced nuclear accumulation of β-catenin and its transcriptional activation, and expression of Wnt target genes are strongly reduced in stable knockdown cell lines deficient for LRP6, Dvl2 or Dvl3. We analysed the H. pylori-induced activation of Wnt-signaling factors and demonstrate for the first time that the canonical Wnt-signaling proteins LRP6 and Dvl2 and Dvl3 are involved in the regulation of β-catenin.
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DOI：
10.1111/j.1349-7006.2002.tb01226.x
发表时间：
2002-11
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Ikenoue T;Ijichi H;Kato N;Kanai F;Masaki T;Rengifo W;Okamoto M;Matsumura M;Kawabe T;Shiratori Y;Omata M
通讯作者：
Omata M
影响因子：
10.5
作者：
Brembeck, FH;Schwarz-Romond, T;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
5.3
作者：
Lustig, B;Jerchow, B;Behrens, J
通讯作者：
Behrens, J
影响因子：
3.9
作者：
Nelson, W. James
通讯作者：
Nelson, W. James
影响因子：
5.3
作者：
Piedra, J;Miravet, S;Duñach, M
通讯作者：
Duñach, M