STAT3-Driven Upregulation of TLR2 Promotes Gastric Tumorigenesis Independent of Tumor Inflammation

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• 作者：Hazel Tye ; Catherine?L. Kennedy ; Meri Najdovska ; Louise McLeod ; William McCormack ; Norman Hughes ; Anouk Dev ; William Sievert ; Chia?Huey Ooi ; Tomo-o Ishikawa ; Hiroko Oshima ; Prithi?S. Bhathal ; Andrew?E. Parker ; Masanobu Oshima ; Patrick Tan ; Brendan?J. Jenkins
• 刊名：Cancer Cell
• 出版年：2012
• 出版时间：16 October, 2012
• 年：2012
• 卷：22
• 期：4
• 页码：466-478
• 全文大小：2064 K

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Summary

Gastric 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.