NOD2 inhibits tumorigenesis and increases chemosensitivity of hepatocellular carcinoma by targeting AMPK pathway.

Cell Death & Disease
Xiaomin MaLihui Han

Abstract

Nucleotide binding oligomerization domain 2 (NOD2) is a recognized innate immune sensor which can initiate potent immune response against pathogens. Many innate immune sensors have been reported to be of great importance in carcinogenesis. However, the role of NOD2 in cancer is not well understood. Here we investigated the role of NOD2 in the development of hepatocellular carcinoma (HCC). We demonstrated that NOD2 deficiency promoted hepatocarcinogenesis in N-nitrosodiethylamine (DEN)/carbon tetrachloride (CCl4) induced HCC mice model and xenograft tumor model. In vitro investigation showed that NOD2 acted as a tumor suppressor and inhibited proliferation, colony formation and invasion of HCC cells. Clinical investigation showed that NOD2 expression was completely lost or significantly downregulated in clinical HCC tissues, and loss of NOD2 expression was significantly correlated with advanced disease stages. Further investigation showed that NOD2 exerted its anti-tumor effect through activating adenosine 5'-monophosphate (AMP) -activated protein kinase (AMPK) signaling pathway, and NOD2 significantly enhanced the sensitivity of HCC cells to sorafenib, lenvatinib and 5-FU treatment through activating AMPK pathway induced apopto...Continue Reading

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Citations

Jun 14, 2020·Signal Transduction and Targeted Therapy·Weiwei TangXuehao Wang
Aug 9, 2020·Cancer Management and Research·Huining TianGuixia Wang
Nov 27, 2020·Scientific Reports·Serdar A GursesDipika Gupta
Mar 14, 2021·Cell Death & Disease·Yafei WuQin Li
Jul 23, 2021·Journal of Chemotherapy·Mandeep Dahiya, Harish Dureja

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Methods Mentioned

BETA
xenograft
PCR
transfection
GTPase
fluorescence activated cell sorting
immunoprecipitation

Key Resources (RRID) Mentioned

CVCL

Software Mentioned

HKGENE
Prism GraphPad
IPP6
Image J
GraphPad

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