Author/Authors :
Tye، نويسنده , , Hazel and Kennedy، نويسنده , , Catherine L. and Najdovska، نويسنده , , Meri and McLeod، نويسنده , , Louise and McCormack، نويسنده , , William and Hughes، نويسنده , , Norman and Dev، نويسنده , , Anouk and Sievert، نويسنده , , William and Ooi، نويسنده , , Chia Huey and Ishikawa، نويسنده , , Tomo-o and Oshima، نويسنده , , Hiroko and Bhathal، نويسنده , , Prithi S. and Parker، نويسنده , , Andrew E. and Oshima، نويسنده , , Masanobu and Tan، نويسنده , , Patrick D. Jenkins، نويسنده , , Brendan J.، نويسنده ,
Abstract :
Summary
c cancer (GC) is associated with chronic inflammation; however, the molecular mechanisms promoting tumorigenesis remain ill defined. Using a GC mouse model driven by hyperactivation of the signal transducer and activator of transcription (STAT)3 oncogene, we show that STAT3 directly upregulates the epithelial expression of the inflammatory mediator Toll-like receptor (TLR)2 in gastric tumors. Genetic and therapeutic targeting of TLR2 inhibited gastric tumorigenesis, but not inflammation, characterized by reduced proliferation and increased apoptosis of the gastric epithelium. Increased STAT3 pathway activation and TLR2 expression were also associated with poor GC patient survival. Collectively, our data reveal an unexpected role for TLR2 in the oncogenic function of STAT3 that may represent a therapeutic target in GC.
