STK4 regulates TLR pathways and protects against chronic inflammation–related hepatocellular carcinoma
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- 英文论文题名：STK4 regulates TLR pathways and protects against chronic inflammation–related hepatocellular carcinoma
- 论文作者：Li Weiyun ; Xiao Jun ; Zhou Xin ; Xu Ming ; Hu Chaobo ; Xu Xiaoyan ; Lu Yao ; Liu Chang ; Xue Shengjie ; Nie Lei ; Zhang Haibin ; Li Zhiqi ; Zhang Yanbo ; Ji Fu ; Hui Lijian ; Tao Wufan ; Wei Bin ; Wang Hongyan
- 英文论文作者：Li Weiyun ; Xiao Jun ; Zhou Xin ; Xu Ming ; Hu Chaobo ; Xu Xiaoyan ; Lu Yao ; Liu Chang ; Xue Shengjie ; Nie Lei ; Zhang Haibin ; Li Zhiqi ; Zhang Yanbo ; Ji Fu ; Hui Lijian ; Tao Wufan ; Wei Bin ; Wang Hongyan ; Institute of Biochemistry and Cell Biology ; Shanghai Institutes for Biological Sciences ; Chinese Academy of Sciences ; Shanghai Jiaotong University ; Hubei Cancer Hospital ; Eastern Hepatobilliary Surgery Hospital ; Fudan University ; Wuhan Institute of Virology
- 年：2016
- 作者机构：Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences;Shanghai Jiaotong University;Hubei Cancer Hospital;Eastern Hepatobilliary Surgery Hospital;Fudan University;Wuhan Institute of Virology;
- 英文论文关键词：stk4 ; IRAK1 ; HCC
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会壁报交流集
- 英文会议录名称：Proceedings of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R735.7
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：2
- 文件大小：323k
- 原文格式：D
- 会议级别：全国
摘要
Hepatocellular carcinoma(HCC) is frequently associated with pathogen infection–induced chronic inflammation.Large numbers of innate immune cells are present in HCCs and can influence disease outcome.Many tumor suppressor genes(TSGs) have been identified in HCC.However,it remains largely unknown which TSGs are critical to preventingchronic inflammation–associated HCC at the early stages.we used 2 murine liver tumor models(DEN-and LPS-induced HCC),as well as human HCC patient samples to check whether and how STK4,a TSG,in macrophages suppresses inflammation and thereby inhibits chronic inflammation–associated HCC.STK4 dampened TLR4/9-induced proinflammatory cytokine secretion but enhanced TLR3/4-triggered IFN-β production via binding to and phosphorylating IL-1 receptor–associated kinase 1(IRAK1),leading to IRAK1 degradation.Moreover,macrophage-specific Stk4 deletion resulted in chronic inflammation,liver fibrosis,and HCC in mice treated with a combination of DEN-and LPS-induced HCC model.In STK4-deficient mice,treatment with an IRAK1/4 inhibitor after DEN administration reduced serum IL-6 levels and liver tumor numbers to levels similar to those observed in the control mice.Together,our results suggest that STK4 has potential as a diagnostic biomarker and therapeutic target for inflammation-induced HCC.
Hepatocellular carcinoma(HCC) is frequently associated with pathogen infection–induced chronic inflammation.Large numbers of innate immune cells are present in HCCs and can influence disease outcome.Many tumor suppressor genes(TSGs) have been identified in HCC.However,it remains largely unknown which TSGs are critical to preventingchronic inflammation–associated HCC at the early stages.we used 2 murine liver tumor models(DEN-and LPS-induced HCC),as well as human HCC patient samples to check whether and how STK4,a TSG,in macrophages suppresses inflammation and thereby inhibits chronic inflammation–associated HCC.STK4 dampened TLR4/9-induced proinflammatory cytokine secretion but enhanced TLR3/4-triggered IFN-β production via binding to and phosphorylating IL-1 receptor–associated kinase 1(IRAK1),leading to IRAK1 degradation.Moreover,macrophage-specific Stk4 deletion resulted in chronic inflammation,liver fibrosis,and HCC in mice treated with a combination of DEN-and LPS-induced HCC model.In STK4-deficient mice,treatment with an IRAK1/4 inhibitor after DEN administration reduced serum IL-6 levels and liver tumor numbers to levels similar to those observed in the control mice.Together,our results suggest that STK4 has potential as a diagnostic biomarker and therapeutic target for inflammation-induced HCC.
Hepatocellular carcinoma(HCC) is frequently associated with pathogen infection–induced chronic inflammation.Large numbers of innate immune cells are present in HCCs and can influence disease outcome.Many tumor suppressor genes(TSGs) have been identified in HCC.However,it remains largely unknown which TSGs are critical to preventingchronic inflammation–associated HCC at the early stages.we used 2 murine liver tumor models(DEN-and LPS-induced HCC),as well as human HCC patient samples to check whether and how STK4,a TSG,in macrophages suppresses inflammation and thereby inhibits chronic inflammation–associated HCC.STK4 dampened TLR4/9-induced proinflammatory cytokine secretion but enhanced TLR3/4-triggered IFN-β production via binding to and phosphorylating IL-1 receptor–associated kinase 1(IRAK1),leading to IRAK1 degradation.Moreover,macrophage-specific Stk4 deletion resulted in chronic inflammation,liver fibrosis,and HCC in mice treated with a combination of DEN-and LPS-induced HCC model.In STK4-deficient mice,treatment with an IRAK1/4 inhibitor after DEN administration reduced serum IL-6 levels and liver tumor numbers to levels similar to those observed in the control mice.Together,our results suggest that STK4 has potential as a diagnostic biomarker and therapeutic target for inflammation-induced HCC.
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