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 TNFα, derived from recruited macrophages, potentiates Wnt/β-catenin signaling and gastric carcinogenesis by activating Akt signaling and GSK3β phosphorylation independent of the NF-κB 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.