2026-03-12T19:30:03Z https://kanazawa-u.repo.nii.ac.jp/oai

oai:kanazawa-u.repo.nii.ac.jp:00027438 2024-06-25T04:59:38Z 1777:1778:1779

Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells. 小熊, 圭祐 大島, 浩子 仲, 一仁 平尾, 敦 大島, 正伸 Oguma, Keisuke 47636 50436804 Oshima, Hiroko 227 80362515 80362515 80362515 Aoki, Masahiro 47716 Uchio, Ryusei 47717 Naka, Kazuhito 274 70372688 70372688 Nakamura, Satoshi 47718 Hirao, Atsushi 30684 90343350 90343350 Saya, Hideyuki 47719 Taketo, Makoto Mark 47720 Oshima, Masanobu 26701 40324610 40324610 40324610 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 journal article Nature Publishing Group 2008-06-18 AM application/pdf The EMBO journal 12 27 1671 1681 1460-2075 https://kanazawa-u.repo.nii.ac.jp/record/27438/files/CA-PR-OSHIMA-M-1671.pdf https://doi.org/10.24517/00027425 http://hdl.handle.net/2297/19676 https://kanazawa-u.repo.nii.ac.jp/records/27438 eng 10.1038/emboj.2008.105