Reference - Detail
| RRC ID | 67959 |
|---|---|
| Author | Oguma K, Oshima H, Aoki M, Uchio R, Naka K, Nakamura S, Hirao A, Saya H, Taketo MM, Oshima M. |
| Title | Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells. |
| Journal | EMBO J |
| Abstract |
The activation of Wnt/beta-catenin signalling has an important function in gastrointestinal tumorigenesis. It has been suggested that the promotion of Wnt/beta-catenin activity beyond the threshold is important for carcinogenesis. We herein investigated the role of macrophages in the promotion of Wnt/beta-catenin activity in gastric tumorigenesis. We found beta-catenin nuclear accumulation in macrophage-infiltrated dysplastic mucosa of the K19-Wnt1 mouse stomach. Moreover, macrophage depletion in Apc(Delta716) mice resulted in the suppression of intestinal tumorigenesis. These results suggested the role of macrophages in the activation of Wnt/beta-catenin signalling, which thus leads to tumour development. Importantly, the conditioned medium of activated macrophages promoted Wnt/beta-catenin signalling in gastric cancer cells, which was suppressed by the inhibition of tumour necrosis factor (TNF)-alpha. Furthermore, treatment with TNF-alpha induced glycogen synthase kinase 3beta (GSK3beta) phosphorylation, which resulted in the stabilization of beta-catenin. We also found that Helicobacter infection in the K19-Wnt1 mouse stomach caused mucosal macrophage infiltration and nuclear beta-catenin accumulation. These results suggest that macrophage-derived TNF-alpha promotes Wnt/beta-catenin signalling through inhibition of GSK3beta, which may contribute to tumour development in the gastric mucosa. |
| Volume | 27(12) |
| Pages | 1671-81 |
| Published | 2008-6-18 |
| DOI | 10.1038/emboj.2008.105 |
| PII | emboj2008105 |
| PMID | 18511911 |
| PMC | PMC2413189 |
| MeSH | Adenomatous Polyposis Coli Protein / metabolism Animals Cell Line, Tumor Cell Nucleus / metabolism Epithelial Cells / microbiology Glycogen Synthase Kinase 3 / antagonists & inhibitors Glycogen Synthase Kinase 3 beta Helicobacter Infections / pathology Humans Macrophage Activation* Mice Mice, Transgenic Mutation / genetics NF-kappa B / metabolism Phosphorylation Precancerous Conditions / enzymology Precancerous Conditions / pathology Signal Transduction* Stomach / microbiology Stomach / pathology Stomach Neoplasms / enzymology Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Tumor Necrosis Factor-alpha / metabolism* Wnt1 Protein / metabolism* beta Catenin / metabolism |
| IF | 9.889 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Wikipedia |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |