桥粒芯蛋白2功能及相关疾病的研究进展
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摘要
桥粒芯蛋白(DSG)是细胞间紧密连接结构之一桥粒的重要组成蛋白,为单次跨膜糖蛋白,与桥粒胶蛋白相互结合,具有调节细胞间黏附、传递胞内外信号等作用。已有研究表明DSG亚型之一DSG2在肿瘤细胞中异常表达,并对肿瘤的靶向治疗及预后有一定价值。文章主要就DSG2蛋白的结构、生物学功能以及相关疾病等进行综述。
Desmoglein(DSG)is an important constituent of desmosome,a single transmembrane glycoprotein that binds to desmocollin(DSC),regulates intercellular adhesion and transmits intracellular and extracelluar signals. Studies have shown that DSG2,one subtype of the DSG,is abnormally expressed in tumor cells and has certain value for targeted treatment and prognosis. This paper reviews the structure,biological functions and related diseases of DSG2 protein.
Desmoglein(DSG)is an important constituent of desmosome,a single transmembrane glycoprotein that binds to desmocollin(DSC),regulates intercellular adhesion and transmits intracellular and extracelluar signals. Studies have shown that DSG2,one subtype of the DSG,is abnormally expressed in tumor cells and has certain value for targeted treatment and prognosis. This paper reviews the structure,biological functions and related diseases of DSG2 protein.
引文
[1]Kim JY,Choi HG,Lee HM,et al.Effects of bisphenol compounds on the growth and epithelial mesenchymal transition of MCF-7 CV human breast cancer cells[J].J Biomed Res,2017,31(4):358-369.
[2]Nitoiu D,Etheridge SL,Kelsell DP.Insights into desmosome biology from inherited human skin disease and cardiocutaneous syndromes[J].Cell Commun Adhes,2014,21(3):129-140.
[3]Celentano A,Cirillo N.Desmosomes in disease:a guide for clinicians[J].Oral Dis,2017,23(2):157-167.
[4]Ishida-Yamamoto A,Igawa S,Kishibe M,et al.Clinical and molecular implications of structural changes to desmosomes and corneodesmosomes[J].J Dermatol,2018,45(4):385-389.
[5]Chen J,Nekrasova OE,Patel DM,et al.The C-terminal unique region of desmoglein 2 inhibits its internalization via tail-tail interactions[J].J Cell Biol,2012,199(4):699-711.
[6]Delva E,Tucker DK,Kowalczyk AP.The Desmosome[J].Cold Spring Harb Perspect Biol,2009,1(2):a2543.
[7]Brown L,Wan H.Desmoglein 3:a help or a hindrance in cancer progression?[J]Cancers(Basel),2015,7(1):266-286.
[8]Nekrasova OE,Amargo EV,Smith WO,et al.Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes[J].J Cell Biol,2011,195(7):1185-1203.
[9]Ishida-Yamamoto A,Igawa S.Genetic skin diseases related to desmosomes and corneodesmosomes[J].J Dermatol Sci,2014,74(2):99-105.
[10]Lowndes M,Rakshit S,Shafraz O,et al.Different roles of cadherins in the assembly and structural integrity of the desmosome complex[J].J Cell Sci,2014,127(Pt 10):2339-2350.
[11]Berika M,Garrod D.Desmosomal adhesion in vivo[J].Cell Commun Adhes,2014,21(1):65-75.
[12]Espana A,Koga H,Suarez-Fernandez R,et al.Antibodies to the amino-terminal domain of desmoglein 1 are retained during transition from pemphigus vulgaris to pemphigus foliaceus[J].Eur J Dermatol,2014,24(2):174-179.
[13]Kasperkiewicz M,Ellebrecht CT,Takahashi H,et al.Pemphigus[J].Nat Rev Dis Primers,2017,3:17026.
[14]Flood K,Stroud C,Lazarov Z,et al.Paraneoplastic pemphigus without antibodies to desmoglein 1 and 3[J].Dermatol Online J,2018,24(2)1-4.
[15]Eshkind L,Tian Q,Schmidt A,et al.Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells[J].Eur J Cell Biol,2002,81(11):592-598.
[16]Koyama-Nasu R,Takahashi R,Yanagida S,et al.The cancer stem cell marker CD133 interacts with plakoglobin and controls desmoglein-2 protein levels[J].PLoS One,2013,8(1):e53710 1-6.
[17]Wei Z,Ma W,Qi X,et al.Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERKsignaling pathway[J].Oncotarget,2016,7(20):29429-29439.
[18]Brennan D,Peltonen S,Dowling A,et al.A role for caveolin-1in desmoglein binding and desmosome dynamics[J].Oncogene,2011,31(13):1636-1648.
[19]Kitajima Y.150(th)anniversary series:Desmosomes and autoimmune disease,perspective of dynamic desmosome remodeling and its impairments in pemphigus[J].Cell Commun Adhes,2014,21(6):269-280.
[20]Kolegraff K,Nava P,Helms MN,et al.Loss of desmocollin-2confers a tumorigenic phenotype to colonic epithelial cells through activation of Akt/beta-catenin signaling[J].Mol Biol Cell,2011,22(8):1121-1134.
[21]Dieding M,Debus JD,Kerkhoff R,et al.Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin binding kinetics[J].Sci Rep,2017,7(1):13791 1-9.
[22]Qadri S,Anttonen O,Viikila J,et al.Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2[J].BMC Med Genet,2017,18(1):86.
[23]郭艳如,郭萍,陈兴,等.DSG2~(F536C)点突变基因敲入小鼠心脏表型的观察研究[J].安徽医药,2017,9:1590-1594.
[24]Liu Y,Chidgey M,Yang VW,et al.Krüppel-like factor 5 is essential for maintenance of barrier function in mouse colon[J].Am J Physiol Gastrointest Liver Physiol,2017,313(5):G478-G491.
[25]Spindler V,Meir M,Vigh B,et al.Loss of Desmoglein 2 Contributes to the Pathogenesis of Crohn's Disease[J].Inflamm Bowel Dis,2015,21(10):2349-2359.
[26]Kiseljak-Vassiliades K,Mills TS,Zhang Y,et al.Elucidating the Role of the Desmosome Protein p53 Apoptosis Effector Related to PMP-22 in Growth Hormone Tumors[J].Endocrinology,2017,158(5):1450-1460.
[27]Green KJ,Gaudry CA.Are desmosomes more than tethers for intermediate filaments[J].Nat Rev Mol Cell Biol,2000,1(3):208-216.
[28]匡小根,张晖辉,许韩峰,等.钙黏蛋白E、桥粒芯糖蛋白2、磷酸化Akt和转录因子Snail在侵袭性前列腺癌中的作用[J].中国现代医学杂志,2016,8:38-43.
[29]Hütz K,Zeiler J,Sachs L,et al.Loss of desmoglein 2 promotes tumorigenic behavior in pancreatic cancer cells[J].Mol Carcinog,2017,56(8):1884-1895.
[30]Ramani VC,Hennings L,Haun RS.Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer[J].BMC Cancer,2008,8:373.
[31]Biedermann K,Vogelsang H,Becker I,et al.Desmoglein 2 is expressed abnormally rather than mutated in familial and sporadic gastric cancer[J].J Pathol,2005,207(2):199-206.
[32]Klessner JL,Desai BV,Amargo EV,et al.EGFR and ADAMs cooperate to regulate shedding and endocytic trafficking of the desmosomal cadherin desmoglein 2[J].Mol Biol Cell,2009,20(1):328-337.
[33]Brennan-Crispi DM,Hossain C,Sahu J,et al.Crosstalk between Desmoglein 2 and Patched 1 accelerates chemical-induced skin tumorigenesis[J].Oncotarget,2015,6(11):8593-8605.
[34]Schneider S,Thurnher D,Kloimstein P,et al.Expression of the Sonic hedgehog pathway in squamous cell carcinoma of the skin and the mucosa of the head and neck[J].Head Neck,2011,33(2):244-250.
[35]Tan LY,Mintoff C,Johan MZ,et al.Desmoglein 2 promotes vasculogenic mimicry in melanoma and is associated with poor clinical outcome[J].Oncotarget,2016,7(29):46492-46508.
[36]Ebert LM,Tan LY,Johan MZ,et al.A non-canonical role for desmoglein-2 in endothelial cells:implications for neoangiogenesis[J].Angiogenesis,2016,19(4):463-486.
[37]Overmiller AM,Pierluissi JA,Wermuth PJ,et al.Desmoglein2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes[J].Faseb J,2017,31(8):3412-3424.
[38]Gornowicz-Porowska J,Bowszyc-Dmochowska M,SeraszekJaros A,et al.Loss of correlation between intensities of desmoglein 2 and desmoglein 3 expression in basal cell carcinomas[J].Acta Dermatovenerol Croat,2011,19(3):150-155.
[39]Kamekura R,Kolegraff KN,Nava P,et al.Loss of the desmosomal cadherin desmoglein-2 suppresses colon cancer cell proliferation through EGFR signaling[J].Oncogene,2013,33(36):4531-4536.
[40]Dusek R L,Attardi LD.Desmosomes:new perpetrators in tumour suppression[J].Nat Rev Cancer,2011,11(5):317-323.
[41]Wang CE,Yumul RC,Lin J,et al.Junction opener protein increases nanoparticle accumulation in solid tumors[J].J Control Release,2018,272:9-16.
[42]Wang H,Yumul R,Cao H,et al.Structural and functional studies on the interaction of adenovirus fiber knobs and desmoglein 2[J].J Virol,2013,87(21):11346-11362.
[43]Yumul R,Richter M,Lu ZZ,et al.Epithelial Junction Opener Improves Oncolytic Adenovirus Therapy in Mouse Tumor Models[J].Hum Gene Ther,2016,27(4):325-337.
[44]Wang H,Ducournau C,Saydaminova K,et al.Intracellular Signaling and Desmoglein 2 Shedding Triggered by Human Adenoviruses Ad3,Ad14,and Ad14P1[J].J Virol,2015,89(21):10841-10859.
[45]Su X,Tian X,Jiang Z,et al.Human Adenovirus Serotype 3Vector Packaged by a Rare Serotype 14 Hexon[J].PLoS One,2016,11(6):e0156984.
[46]庞小娟,李晓军,秦浚川.腺病毒载体纯化及在肿瘤基因治疗中的应用[J].医学研究生学报,2009,22(12):1324-1327.
[47]王利平,包晓辰,魏玮,等.携带可诱导共刺激分子基因的重组腺病毒载体构建及其在小鼠间充质干细胞中的表达[J].医学研究生学报,2012,25(9):909-914.
[2]Nitoiu D,Etheridge SL,Kelsell DP.Insights into desmosome biology from inherited human skin disease and cardiocutaneous syndromes[J].Cell Commun Adhes,2014,21(3):129-140.
[3]Celentano A,Cirillo N.Desmosomes in disease:a guide for clinicians[J].Oral Dis,2017,23(2):157-167.
[4]Ishida-Yamamoto A,Igawa S,Kishibe M,et al.Clinical and molecular implications of structural changes to desmosomes and corneodesmosomes[J].J Dermatol,2018,45(4):385-389.
[5]Chen J,Nekrasova OE,Patel DM,et al.The C-terminal unique region of desmoglein 2 inhibits its internalization via tail-tail interactions[J].J Cell Biol,2012,199(4):699-711.
[6]Delva E,Tucker DK,Kowalczyk AP.The Desmosome[J].Cold Spring Harb Perspect Biol,2009,1(2):a2543.
[7]Brown L,Wan H.Desmoglein 3:a help or a hindrance in cancer progression?[J]Cancers(Basel),2015,7(1):266-286.
[8]Nekrasova OE,Amargo EV,Smith WO,et al.Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes[J].J Cell Biol,2011,195(7):1185-1203.
[9]Ishida-Yamamoto A,Igawa S.Genetic skin diseases related to desmosomes and corneodesmosomes[J].J Dermatol Sci,2014,74(2):99-105.
[10]Lowndes M,Rakshit S,Shafraz O,et al.Different roles of cadherins in the assembly and structural integrity of the desmosome complex[J].J Cell Sci,2014,127(Pt 10):2339-2350.
[11]Berika M,Garrod D.Desmosomal adhesion in vivo[J].Cell Commun Adhes,2014,21(1):65-75.
[12]Espana A,Koga H,Suarez-Fernandez R,et al.Antibodies to the amino-terminal domain of desmoglein 1 are retained during transition from pemphigus vulgaris to pemphigus foliaceus[J].Eur J Dermatol,2014,24(2):174-179.
[13]Kasperkiewicz M,Ellebrecht CT,Takahashi H,et al.Pemphigus[J].Nat Rev Dis Primers,2017,3:17026.
[14]Flood K,Stroud C,Lazarov Z,et al.Paraneoplastic pemphigus without antibodies to desmoglein 1 and 3[J].Dermatol Online J,2018,24(2)1-4.
[15]Eshkind L,Tian Q,Schmidt A,et al.Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells[J].Eur J Cell Biol,2002,81(11):592-598.
[16]Koyama-Nasu R,Takahashi R,Yanagida S,et al.The cancer stem cell marker CD133 interacts with plakoglobin and controls desmoglein-2 protein levels[J].PLoS One,2013,8(1):e53710 1-6.
[17]Wei Z,Ma W,Qi X,et al.Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERKsignaling pathway[J].Oncotarget,2016,7(20):29429-29439.
[18]Brennan D,Peltonen S,Dowling A,et al.A role for caveolin-1in desmoglein binding and desmosome dynamics[J].Oncogene,2011,31(13):1636-1648.
[19]Kitajima Y.150(th)anniversary series:Desmosomes and autoimmune disease,perspective of dynamic desmosome remodeling and its impairments in pemphigus[J].Cell Commun Adhes,2014,21(6):269-280.
[20]Kolegraff K,Nava P,Helms MN,et al.Loss of desmocollin-2confers a tumorigenic phenotype to colonic epithelial cells through activation of Akt/beta-catenin signaling[J].Mol Biol Cell,2011,22(8):1121-1134.
[21]Dieding M,Debus JD,Kerkhoff R,et al.Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin binding kinetics[J].Sci Rep,2017,7(1):13791 1-9.
[22]Qadri S,Anttonen O,Viikila J,et al.Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2[J].BMC Med Genet,2017,18(1):86.
[23]郭艳如,郭萍,陈兴,等.DSG2~(F536C)点突变基因敲入小鼠心脏表型的观察研究[J].安徽医药,2017,9:1590-1594.
[24]Liu Y,Chidgey M,Yang VW,et al.Krüppel-like factor 5 is essential for maintenance of barrier function in mouse colon[J].Am J Physiol Gastrointest Liver Physiol,2017,313(5):G478-G491.
[25]Spindler V,Meir M,Vigh B,et al.Loss of Desmoglein 2 Contributes to the Pathogenesis of Crohn's Disease[J].Inflamm Bowel Dis,2015,21(10):2349-2359.
[26]Kiseljak-Vassiliades K,Mills TS,Zhang Y,et al.Elucidating the Role of the Desmosome Protein p53 Apoptosis Effector Related to PMP-22 in Growth Hormone Tumors[J].Endocrinology,2017,158(5):1450-1460.
[27]Green KJ,Gaudry CA.Are desmosomes more than tethers for intermediate filaments[J].Nat Rev Mol Cell Biol,2000,1(3):208-216.
[28]匡小根,张晖辉,许韩峰,等.钙黏蛋白E、桥粒芯糖蛋白2、磷酸化Akt和转录因子Snail在侵袭性前列腺癌中的作用[J].中国现代医学杂志,2016,8:38-43.
[29]Hütz K,Zeiler J,Sachs L,et al.Loss of desmoglein 2 promotes tumorigenic behavior in pancreatic cancer cells[J].Mol Carcinog,2017,56(8):1884-1895.
[30]Ramani VC,Hennings L,Haun RS.Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer[J].BMC Cancer,2008,8:373.
[31]Biedermann K,Vogelsang H,Becker I,et al.Desmoglein 2 is expressed abnormally rather than mutated in familial and sporadic gastric cancer[J].J Pathol,2005,207(2):199-206.
[32]Klessner JL,Desai BV,Amargo EV,et al.EGFR and ADAMs cooperate to regulate shedding and endocytic trafficking of the desmosomal cadherin desmoglein 2[J].Mol Biol Cell,2009,20(1):328-337.
[33]Brennan-Crispi DM,Hossain C,Sahu J,et al.Crosstalk between Desmoglein 2 and Patched 1 accelerates chemical-induced skin tumorigenesis[J].Oncotarget,2015,6(11):8593-8605.
[34]Schneider S,Thurnher D,Kloimstein P,et al.Expression of the Sonic hedgehog pathway in squamous cell carcinoma of the skin and the mucosa of the head and neck[J].Head Neck,2011,33(2):244-250.
[35]Tan LY,Mintoff C,Johan MZ,et al.Desmoglein 2 promotes vasculogenic mimicry in melanoma and is associated with poor clinical outcome[J].Oncotarget,2016,7(29):46492-46508.
[36]Ebert LM,Tan LY,Johan MZ,et al.A non-canonical role for desmoglein-2 in endothelial cells:implications for neoangiogenesis[J].Angiogenesis,2016,19(4):463-486.
[37]Overmiller AM,Pierluissi JA,Wermuth PJ,et al.Desmoglein2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes[J].Faseb J,2017,31(8):3412-3424.
[38]Gornowicz-Porowska J,Bowszyc-Dmochowska M,SeraszekJaros A,et al.Loss of correlation between intensities of desmoglein 2 and desmoglein 3 expression in basal cell carcinomas[J].Acta Dermatovenerol Croat,2011,19(3):150-155.
[39]Kamekura R,Kolegraff KN,Nava P,et al.Loss of the desmosomal cadherin desmoglein-2 suppresses colon cancer cell proliferation through EGFR signaling[J].Oncogene,2013,33(36):4531-4536.
[40]Dusek R L,Attardi LD.Desmosomes:new perpetrators in tumour suppression[J].Nat Rev Cancer,2011,11(5):317-323.
[41]Wang CE,Yumul RC,Lin J,et al.Junction opener protein increases nanoparticle accumulation in solid tumors[J].J Control Release,2018,272:9-16.
[42]Wang H,Yumul R,Cao H,et al.Structural and functional studies on the interaction of adenovirus fiber knobs and desmoglein 2[J].J Virol,2013,87(21):11346-11362.
[43]Yumul R,Richter M,Lu ZZ,et al.Epithelial Junction Opener Improves Oncolytic Adenovirus Therapy in Mouse Tumor Models[J].Hum Gene Ther,2016,27(4):325-337.
[44]Wang H,Ducournau C,Saydaminova K,et al.Intracellular Signaling and Desmoglein 2 Shedding Triggered by Human Adenoviruses Ad3,Ad14,and Ad14P1[J].J Virol,2015,89(21):10841-10859.
[45]Su X,Tian X,Jiang Z,et al.Human Adenovirus Serotype 3Vector Packaged by a Rare Serotype 14 Hexon[J].PLoS One,2016,11(6):e0156984.
[46]庞小娟,李晓军,秦浚川.腺病毒载体纯化及在肿瘤基因治疗中的应用[J].医学研究生学报,2009,22(12):1324-1327.
[47]王利平,包晓辰,魏玮,等.携带可诱导共刺激分子基因的重组腺病毒载体构建及其在小鼠间充质干细胞中的表达[J].医学研究生学报,2012,25(9):909-914.