@article{oai:kanazawa-u.repo.nii.ac.jp:00027438,
 author = {小熊, 圭祐 and 大島, 浩子 and 仲, 一仁 and 平尾, 敦 and 大島, 正伸 and Oguma, Keisuke and Oshima, Hiroko and Aoki, Masahiro and Uchio, Ryusei and Naka, Kazuhito and Nakamura, Satoshi and Hirao, Atsushi and Saya, Hideyuki and Taketo, Makoto Mark and Oshima, Masanobu},
 issue = {12},
 journal = {The EMBO journal},
 month = {Jun},
 note = {The activation of Wnt/β-catenin signalling has an important function in gastrointestinal tumorigenesis. It has been suggested that the promotion of Wnt/β-catenin activity beyond the threshold is important for carcinogenesis. We herein investigated the role of macrophages in the promotion of Wnt/β-catenin activity in gastric tumorigenesis. We found β-catenin nuclear accumulation in macrophage-infiltrated dysplastic mucosa of the K19-Wnt1 mouse stomach. Moreover, macrophage depletion in Apc Δ716 mice resulted in the suppression of intestinal tumorigenesis. These results suggested the role of macrophages in the activation of Wnt/β-catenin signalling, which thus leads to tumour development. Importantly, the conditioned medium of activated macrophages promoted Wnt/β-catenin signalling in gastric cancer cells, which was suppressed by the inhibition of tumour necrosis factor (TNF)-α. Furthermore, treatment with TNF-α induced glycogen synthase kinase 3β (GSK3β) phosphorylation, which resulted in the stabilization of β-catenin. We also found that Helicobacter infection in the K19-Wnt1 mouse stomach caused mucosal macrophage infiltration and nuclear β-catenin accumulation. These results suggest that macrophage-derived TNF-α promotes Wnt/β-catenin signalling through inhibition of GSK3β, which may contribute to tumour development in the gastric mucosa. © 2008 European Molecular Biology Organization | All Rights Reserved., 金沢大学がん研究所がん幹細胞研究センター},
 pages = {1671--1681},
 title = {Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells.},
 volume = {27},
 year = {2008}
}