Zhuo Wang
Southern University of Science and Technology, China
Title: Stat3 tyrosine phosphorylation is critical for hepatocellular carcinoma proliferation, survival and angiogenesis in response to lipopolysaccharide
Biography
Biography: Zhuo Wang
Abstract
Hepatocellular carcinoma (HCC) is a long-term sequence of chronic inflammatory liver injury and hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products including lipopolysaccharide (LPS), which promotes hepatocarcinogenesis. Despite its clinical signiï¬cance, mediators responsible for the high risk of inflammation to develop HCC in the chronically injured liver remain to be clarified. Here, we report a novel mechanism by which LPS/signal transducer and activator of transcription 3 (STAT3) signaling promotes the angiogenesis in HCC both in vitro and in vivo. STAT3 activated by LPS increases the production of vascular endothelial growth factor (VEGF) by tumor cells, which in turn stimulates the migration and tubulogenesis of endothelial cells through STAT3 activation and hence promotes angiogenesis in HCC. Moreover, our data suggested that hypoxia-induced VEGF expression, which also contributes to angiogenesis in HCC, was in a STAT3-dependent pathway. Our findings not only provide a potential mechanism by which bacterial infection enhances HCC oncogenesis through promoting the angiogenesis in liver, but also suggest that targeting STAT3 might be an effective therapeutic strategy in HCC treatment considering the dual roles of STAT3 in angiogenesis.