NOD样受体介导的信号转导通路及其与肿瘤关系的研究进展
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摘要
核苷酸结合寡聚化结构域(nucleotide-binding oligomerization domain,NOD)样受体是一类位于细胞质的模式识别受体,在先天性免疫应答中起着十分重要的作用。NOD样受体被激活后,通过一系列的信号通路,能诱导各种炎症因子的释放。从NOD样受体的组成、NOD样受体介导的信号转导通路以及NOD样受体与肿瘤关系3个方面进行了综述。
Nucleotide-binding oligomerization domain(NOD)-like receptor, a member of pathogen recognition receptors existing in the cytoplasm, is of vital importance to innate immunity. NOD-like receptor is activated, it wil induce the release of plenty of inflammatory factors through a variety of signaling pathways. This review presents the constitution of NOD-like receptor, NODmediated signaling pathways and the relationship between NOD-like receptor and tumors.
Nucleotide-binding oligomerization domain(NOD)-like receptor, a member of pathogen recognition receptors existing in the cytoplasm, is of vital importance to innate immunity. NOD-like receptor is activated, it wil induce the release of plenty of inflammatory factors through a variety of signaling pathways. This review presents the constitution of NOD-like receptor, NODmediated signaling pathways and the relationship between NOD-like receptor and tumors.
引文
[1]TAKEUCHI O,AKIRA S.Pattern recognition receptors and inflammation[J].Cell,2010,140(6):805-820.
[2]MOTTA V,SOARES F,SUN T,et al.NOD-like receptors:versatile cytosolic sentinels[J].Physiol Rev,2015,95(1):149-178.
[3]INOHARA N,NUNEZ G.NODs:intracellular proteins involved in inflammation and apoptosis[J].Nat Rev Immunol,2003,3(5):371-382.
[4]CHAMAILLARD M,FUKASE K,NU?EZ G,et al.An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid[J].Nat Immunol,2003,4(7):702-707.
[5]GIRARDIN S E,BONECA I G,LETICIA A M C,et al.Nod1detects a unique muropeptide from gram-negative bacterial peptidoglycan[J].Science,2003,300(5625):1584-1587.
[6]GIRARDIN S E,BONECA I G,VIALA J R M,et al.Nod2 is a general sensor of peptidoglycan through muramyl dipeptide(MDP)detection[J].J Biol Chem,2003,278(11):8869-8872.
[7]INOHARA N,OGURA Y,FONTALBA A,et al.Host recognition of bacterial muramyl dipeptide mediated through NOD2[J].J Biol Chem,2003,8(278):5509-5512.
[8]SABBAH A,CHANG T H,HARNACK R,et al.Activation of innate immune antiviral responses by Nod2[J].Nat Immunol,2009,10(10):1073-1080.
[9]GIRARDIN S E,TOURNEBIZE R,MAVRIS M,et al.CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri[J].EMBO Rep,2001,2(8):736-742.
[10]PARK J,KIM Y,MCDONALD C,et al.RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs[J].J Immunol,2007,178(4):2380-2386.
[11]BERTRAND M J M,DOIRON K,LABBéK,et al.Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1and NOD2[J].Immunity,2009,30(6):789-801.
[12]KRIEG A,CORREA R G,GARRISON J B,et al.XIAPmediates NOD signaling via interaction with RIP2[J].Proc Natl Acad Sci U S A,2009,106(34):14524-14529.
[13]HASEGAWA M,FUJIMOTO Y,LUCAS P C,et al.A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation[J].EMBO J,2008,27(2):373-383.
[14]YOU Y,LI H,QIN X,et al.The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens[J].Nat Immunol,2007,8(2):198-205.
[15]JONES N L,PHILPOTT D J,SOARES F,et al.Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry[J].Nat Immunol,2010,11(1):55-62.
[16]ALLAN P,SIMMONS A,COONEY R,et al.NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation[J].Nat Med,2010,16(1):90-97.
[17]HOMER C R,RICHMOND A L,REBERT N A,et al.ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn’s disease pathogenesis[J].Gastroenterology,2010,139(5):1630-1641.
[18]DE JONG M F,SUN Y,DEN HARTIGH A B,et al.Identification of VceA and VceC,two members of the VjbRregulon that are translocated into macrophages by the Brucella typeⅣsecretion system[J].Mol Microbiol,2008,70(6):1378-1396.
[19]DE JONG M F,STARR T,WINTER M G,et al.Sensing of bacterial typeⅣsecretion via the unfolded protein response[J].MBio,2013,4(1):e00418-12.
[20]BYNDLOSS M X,KEESTRA-GOUNDER A M,B?UMLER AJ,et al.NOD1 and NOD2:new functions linking endoplasmic reticulum stress and inflammation[J].DNA Cell Biol,2016,35(7):311-313.
[21]URANO F,WANG X,BERTOLOTTI A,et al.Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1[J].Science,2000,287(5453):664-666.
[22]VAN BEELEN A J,ZELINKOVA Z,TAANMAN-KUETER EW,et al.Stimulation of the intracellular bacterial sensor NOD2programs dendritic cells to promote interleukin-17 production in human memory T cells[J].Immunity,2007,27(4):660-669.
[23]DONG W,ZHANG H,YIN X,et al.Oral delivery of tumor microparticle vaccines activates NOD2 signaling pathway in ileac epithelium rendering potent antitumor T cell immunity[J].Oncoimmunology,2017,6(3):e1282589.
[24]FRITZ J H,LE BOURHIS L,SELLGE G,et al.Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity[J].Immunity,2007,26(4):445-459.
[25]MAGALHAES J G,FRITZ J H,LE BOURHIS L,et al.Nod2-dependent Th2 polarization of antigen-specific immunity[J].J Immunol,2008,181(11):7925-7935.
[26]LIU S,CAI X,WU J,et al.Phosphorylation of innate immune adaptor proteins MAVS,STING,and TRIF induces IRF3activation[J].Science,2015,347(6227):a2630.
[27]FANG R,JIANG Q,ZHOU X,et al.MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner[J].PLoS Pathog,2017,13(11):e1006720.
[28]KORNILUK A,KOPER O,KEMONA H,et al.From inflammation to cancer[J].Ir J Med Sci,2017,186(1):57-62.
[29]DA SILVA CORREIA J,MIRANDA Y,AUSTIN-BROWN N,et al.Nod1-dependent control of tumor growth[J].Proc Natl Acad Sci U S A,2006,103(6):1840-1845.
[30]CHAN L,WANG L,CHIANG F,et al.IL-8 promotes HNSCCprogression on CXCR1/2-meidated NOD1/RIP2 signaling pathway[J].Oncotarget,2016,7(38):61820-61831.
[31]YOON H E,AHN M Y,KWON S M,et al.Nucleotide-binding oligomerization domain 2(NOD2)activation induces apoptosis of human oral squamous cell carcinoma cells[J].J Oral Pathol Med,2016,45(4):262-267.
[32]COUTURIER-MAILLARD A,SECHER T,REHMAN A,et al.NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer[J].J Clin Invest,2013,123(2):700-711.
[33]UDDEN S M N,PENG L,GAN J,et al.NOD2 suppresses colorectal tumorigenesis via downregulation of the TLR pathways[J].Cell Rep,2017,19(13):2756-2770.
[34]SUAREZ G,ROMERO-GALLO J,PIAZUELO M B,et al.Modification of Helicobacter pylori peptidoglycan enhances NOD1 activation and promotes cancer of the stomach[J].Cancer Res,2015,75(8):1749-1759.
[35]ALLISON C C,FERRAND J,MCLEOD L,et al.Nucleotide oligomerization domain 1 enhances IFN-γsignaling in gastric epithelial cells during Helicobacter pylori infection and exacerbates disease severity[J].J Immunol,2013,190(7):3706-3715.
[36]SINGEL S,BATTEN K,CORNELIUS C,et al.Receptorinteracting protein kinase 2 promotes triple-negative breast cancer cell migration and invasion via activation of nuclear factor-kappaB and c-Jun N-terminal kinase pathways[J].Breast Cancer Res,2014,16(2):R28.
[37]ZARE A,PETROVA A,AGOUMI M,et al.RIPK2:new elements in modulating inflammatory breast cancer pathogenesis[J].Cancers,2018,10(6):E184.
[38]ZHANG H,CHIN A I.Role of Rip2 in development of tumorinfiltrating MDSCs and bladder cancer metastasis[J].PLoSOne,2014,9(4):e94793.
[39]ZHAN Y,SEREGIN S S,CHEN J,et al.Nod1 limits colitisassociated tumorigenesis by regulating IFN-γproduction[J].J Immunol,2016,196(12):5121-5129.
[40]AMIRI R M,TEHRANI M,TAGHIZADEH S,et al.Association of nucleotide-binding oligomerization domain receptors with peptic ulcer and gastric cancer[J].Iran J Allergy Asthma Immunol,2016,15(5):355-362.
[41]XU D,ZHANG S,ZHANG S,et al.NOD2 maybe a biomarker for the survival of kidney cancer patients[J].Oncotarget,2017,8(60):101489-101499.
[42]WANG S,YAN G J,LIX,et al.Discovery of 1,4-benzodiazepine-2,5-dione(BZD)derivatives as dual nucleotide binding oligomerization domain containing 1/2(NOD1/NOD2)antagonists sensitizing paclitaxel(PTX)to suppress Lewis lung carcinoma(LLC)growth in vivo[J].JMed Chem,2017,60(12):5162-5192.
[43]GUO X,LI X,ZHOU P,et al.Evodiamine induces apoptosis in SMMC-7721 and HepG2 cells by suppressing NOD1 signal pathway[J].Int J Mol Sci,2018,19(11):E3419.
[2]MOTTA V,SOARES F,SUN T,et al.NOD-like receptors:versatile cytosolic sentinels[J].Physiol Rev,2015,95(1):149-178.
[3]INOHARA N,NUNEZ G.NODs:intracellular proteins involved in inflammation and apoptosis[J].Nat Rev Immunol,2003,3(5):371-382.
[4]CHAMAILLARD M,FUKASE K,NU?EZ G,et al.An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid[J].Nat Immunol,2003,4(7):702-707.
[5]GIRARDIN S E,BONECA I G,LETICIA A M C,et al.Nod1detects a unique muropeptide from gram-negative bacterial peptidoglycan[J].Science,2003,300(5625):1584-1587.
[6]GIRARDIN S E,BONECA I G,VIALA J R M,et al.Nod2 is a general sensor of peptidoglycan through muramyl dipeptide(MDP)detection[J].J Biol Chem,2003,278(11):8869-8872.
[7]INOHARA N,OGURA Y,FONTALBA A,et al.Host recognition of bacterial muramyl dipeptide mediated through NOD2[J].J Biol Chem,2003,8(278):5509-5512.
[8]SABBAH A,CHANG T H,HARNACK R,et al.Activation of innate immune antiviral responses by Nod2[J].Nat Immunol,2009,10(10):1073-1080.
[9]GIRARDIN S E,TOURNEBIZE R,MAVRIS M,et al.CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri[J].EMBO Rep,2001,2(8):736-742.
[10]PARK J,KIM Y,MCDONALD C,et al.RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs[J].J Immunol,2007,178(4):2380-2386.
[11]BERTRAND M J M,DOIRON K,LABBéK,et al.Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1and NOD2[J].Immunity,2009,30(6):789-801.
[12]KRIEG A,CORREA R G,GARRISON J B,et al.XIAPmediates NOD signaling via interaction with RIP2[J].Proc Natl Acad Sci U S A,2009,106(34):14524-14529.
[13]HASEGAWA M,FUJIMOTO Y,LUCAS P C,et al.A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation[J].EMBO J,2008,27(2):373-383.
[14]YOU Y,LI H,QIN X,et al.The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens[J].Nat Immunol,2007,8(2):198-205.
[15]JONES N L,PHILPOTT D J,SOARES F,et al.Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry[J].Nat Immunol,2010,11(1):55-62.
[16]ALLAN P,SIMMONS A,COONEY R,et al.NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation[J].Nat Med,2010,16(1):90-97.
[17]HOMER C R,RICHMOND A L,REBERT N A,et al.ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn’s disease pathogenesis[J].Gastroenterology,2010,139(5):1630-1641.
[18]DE JONG M F,SUN Y,DEN HARTIGH A B,et al.Identification of VceA and VceC,two members of the VjbRregulon that are translocated into macrophages by the Brucella typeⅣsecretion system[J].Mol Microbiol,2008,70(6):1378-1396.
[19]DE JONG M F,STARR T,WINTER M G,et al.Sensing of bacterial typeⅣsecretion via the unfolded protein response[J].MBio,2013,4(1):e00418-12.
[20]BYNDLOSS M X,KEESTRA-GOUNDER A M,B?UMLER AJ,et al.NOD1 and NOD2:new functions linking endoplasmic reticulum stress and inflammation[J].DNA Cell Biol,2016,35(7):311-313.
[21]URANO F,WANG X,BERTOLOTTI A,et al.Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1[J].Science,2000,287(5453):664-666.
[22]VAN BEELEN A J,ZELINKOVA Z,TAANMAN-KUETER EW,et al.Stimulation of the intracellular bacterial sensor NOD2programs dendritic cells to promote interleukin-17 production in human memory T cells[J].Immunity,2007,27(4):660-669.
[23]DONG W,ZHANG H,YIN X,et al.Oral delivery of tumor microparticle vaccines activates NOD2 signaling pathway in ileac epithelium rendering potent antitumor T cell immunity[J].Oncoimmunology,2017,6(3):e1282589.
[24]FRITZ J H,LE BOURHIS L,SELLGE G,et al.Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity[J].Immunity,2007,26(4):445-459.
[25]MAGALHAES J G,FRITZ J H,LE BOURHIS L,et al.Nod2-dependent Th2 polarization of antigen-specific immunity[J].J Immunol,2008,181(11):7925-7935.
[26]LIU S,CAI X,WU J,et al.Phosphorylation of innate immune adaptor proteins MAVS,STING,and TRIF induces IRF3activation[J].Science,2015,347(6227):a2630.
[27]FANG R,JIANG Q,ZHOU X,et al.MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner[J].PLoS Pathog,2017,13(11):e1006720.
[28]KORNILUK A,KOPER O,KEMONA H,et al.From inflammation to cancer[J].Ir J Med Sci,2017,186(1):57-62.
[29]DA SILVA CORREIA J,MIRANDA Y,AUSTIN-BROWN N,et al.Nod1-dependent control of tumor growth[J].Proc Natl Acad Sci U S A,2006,103(6):1840-1845.
[30]CHAN L,WANG L,CHIANG F,et al.IL-8 promotes HNSCCprogression on CXCR1/2-meidated NOD1/RIP2 signaling pathway[J].Oncotarget,2016,7(38):61820-61831.
[31]YOON H E,AHN M Y,KWON S M,et al.Nucleotide-binding oligomerization domain 2(NOD2)activation induces apoptosis of human oral squamous cell carcinoma cells[J].J Oral Pathol Med,2016,45(4):262-267.
[32]COUTURIER-MAILLARD A,SECHER T,REHMAN A,et al.NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer[J].J Clin Invest,2013,123(2):700-711.
[33]UDDEN S M N,PENG L,GAN J,et al.NOD2 suppresses colorectal tumorigenesis via downregulation of the TLR pathways[J].Cell Rep,2017,19(13):2756-2770.
[34]SUAREZ G,ROMERO-GALLO J,PIAZUELO M B,et al.Modification of Helicobacter pylori peptidoglycan enhances NOD1 activation and promotes cancer of the stomach[J].Cancer Res,2015,75(8):1749-1759.
[35]ALLISON C C,FERRAND J,MCLEOD L,et al.Nucleotide oligomerization domain 1 enhances IFN-γsignaling in gastric epithelial cells during Helicobacter pylori infection and exacerbates disease severity[J].J Immunol,2013,190(7):3706-3715.
[36]SINGEL S,BATTEN K,CORNELIUS C,et al.Receptorinteracting protein kinase 2 promotes triple-negative breast cancer cell migration and invasion via activation of nuclear factor-kappaB and c-Jun N-terminal kinase pathways[J].Breast Cancer Res,2014,16(2):R28.
[37]ZARE A,PETROVA A,AGOUMI M,et al.RIPK2:new elements in modulating inflammatory breast cancer pathogenesis[J].Cancers,2018,10(6):E184.
[38]ZHANG H,CHIN A I.Role of Rip2 in development of tumorinfiltrating MDSCs and bladder cancer metastasis[J].PLoSOne,2014,9(4):e94793.
[39]ZHAN Y,SEREGIN S S,CHEN J,et al.Nod1 limits colitisassociated tumorigenesis by regulating IFN-γproduction[J].J Immunol,2016,196(12):5121-5129.
[40]AMIRI R M,TEHRANI M,TAGHIZADEH S,et al.Association of nucleotide-binding oligomerization domain receptors with peptic ulcer and gastric cancer[J].Iran J Allergy Asthma Immunol,2016,15(5):355-362.
[41]XU D,ZHANG S,ZHANG S,et al.NOD2 maybe a biomarker for the survival of kidney cancer patients[J].Oncotarget,2017,8(60):101489-101499.
[42]WANG S,YAN G J,LIX,et al.Discovery of 1,4-benzodiazepine-2,5-dione(BZD)derivatives as dual nucleotide binding oligomerization domain containing 1/2(NOD1/NOD2)antagonists sensitizing paclitaxel(PTX)to suppress Lewis lung carcinoma(LLC)growth in vivo[J].JMed Chem,2017,60(12):5162-5192.
[43]GUO X,LI X,ZHOU P,et al.Evodiamine induces apoptosis in SMMC-7721 and HepG2 cells by suppressing NOD1 signal pathway[J].Int J Mol Sci,2018,19(11):E3419.