Inflaming gastrointestinal oncogenic programming.
The etiology of gastrointestinal tumors implicates a role for chronic inflammation in response to pathogenic microflora as a promoting force for full neoplastic progression. Recently, Oguma and coworkers (2008) demonstrated that TNFalpha, derived from recruited macrophages, potentiates Wnt/beta-catenin signaling and gastric carcinogenesis by activating Akt signaling and GSK3beta phosphorylation independent of the NF-kappaB pathway in initiated epithelial cells. These observations provide a missing link in the mechanism whereby chronic inflammation, in response to Helicobacter, regulates the "penetrance" of initiating oncogenic mutations in the gastrointestinal tract leading to gastrointestinal tumorigenesis.
DeNardo
David G
DG
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Johansson
Magnus
M
Coussens
Lisa M
LM
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology; D005756:Gastritis / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000382:microbiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3