What lurks beneath: IL-11, via Stat3, promotes inflammation-associated gastric tumorigenesis.
Chronic inflammation in the stomach induces cellular transformation and gastric cancer primarily in the distal stomach or antrum. In this issue of the JCI, a study in mice by Ernst et al. provides new insight into the role of IL-11 and its glycoprotein 130 (gp130) receptor in inflammation-associated gastric epithelial cell oncogenic transformation, which they show is mediated by and dependent on increased activation of Stat3 and, to a lesser extent, Stat1 (see the related article beginning on page 1727). Prior studies from this group have shown that Stat3 hyperactivity stimulates the TGF-beta inhibitor Smad7. Collectively, the studies suggest that an important pathway of oncogenic transformation in the stomach is through suppression of growth inhibitory signals, such as members of the TGF-beta family, that originate from the stroma.
Merchant
Juanita L
JL
Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB Room 2051, Ann Arbor, Michigan 48198-2200, USA. merchanj@umich.edu
D000818:Animals; D002471:Cell Transformation, Neoplastic; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000276:immunology; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D017370:Interleukin-11 / Q000276:immunology*; D051379:Mice; D050796:STAT3 Transcription Factor / Q000276:immunology*; D051906:Smad7 Protein / Q000276:immunology; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology
D017370:Interleukin-11; D050796:STAT3 Transcription Factor; D051906:Smad7 Protein; D050822:Cytokine Receptor gp130