{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:56:58Z","timestamp":1791205018391,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,8,24]],"date-time":"2007-08-24T00:00:00Z","timestamp":1187913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Health and Medical Research Council of Australia"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection accounts for most cases of gastric cancer, but the initiating events remain unclear. The principal\n                    <jats:italic>H. pylori<\/jats:italic>\n                    pathogenicity\u2010associated CagA protein disrupts intracellular SHP\u20102 signalling pathways including those used by the IL\u20106 family cytokines, IL\u20106 and IL\u201011. Imbalanced IL\u20106 family cytokine signalling in the gp130\n                    <jats:sup>757FF<\/jats:sup>\n                    mouse model of gastric cancer arising from hyperactivation of oncogenic STAT3 after altered SHP\u20102 : ERK1\/2 signalling produces dysplastic antral tumours preceded by gastritis and metaplasia. In a cohort of patient gastric biopsies with known\n                    <jats:italic>H. pylori<\/jats:italic>\n                    and CagA status, we investigated whether (i) STAT3 and ERK1\/2 activation is altered in\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2010dependent gastritis; (ii) these profiles are more pronounced in CagA+\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection; and (iii) the expression of pro\u2010inflammatory cytokines that activate STAT3 and ERK 1\/2 pathways is associated with progression to gastric cancer. IL\u20106, IL\u201011, and activated STAT3 and ERK1\/2 were quantified in antral biopsies from gastritic stomach, metaplastic tissue, and resected gastric cancer tissues. We observed significantly increased STAT3 and ERK1\/2 activation (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.001) in\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2010dependent gastritis, which was further enhanced in the presence of CagA+\n                    <jats:italic>H. pylori<\/jats:italic>\n                    strains. Of known gastric ligands that drive STAT3 activation, IL\u20106 expression was increased after\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection and both IL\u20106 and IL\u201011 were strongly up\u2010regulated in the gastric cancer biopsies. This suggests a mechanism by which IL\u201011 drives STAT3 activation and proliferation during gastric cancer progression. We addressed this using an\n                    <jats:italic>in vitro<\/jats:italic>\n                    approach, demonstrating that recombinant human IL\u201011 activates STAT3 and concomitantly increases proliferation of MKN28 gastric epithelial cells. In summary, we show increased STAT3 and ERK1\/2 activation in\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2010dependent gastritis that is likely driven in an IL\u20106\u2010dependent fashion. IL\u201011 expression is associated with adenocarcinoma development, but not gastritic lesions, and we identify a novel mechanism for IL\u201011 as a potent inducer of proliferation in the human gastric cancer setting. Copyright \u00a9 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2218","type":"journal-article","created":{"date-parts":[[2007,8,27]],"date-time":"2007-08-27T17:16:48Z","timestamp":1188235008000},"page":"140-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Augmented gp130\u2010mediated cytokine signalling accompanies human gastric cancer 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