Ezrin蛋白与消化系统恶性肿瘤关系的研究进展
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摘要
Ezrin蛋白作为ERM(Ezrin,Radixin,Moesin)家族的重要成员,其主要作用是参与细胞膜信号转导,维持细胞形态、运动和黏附,重塑细胞骨架等,还起到连接细胞膜和细胞骨架的作用。Ezrin蛋白在肿瘤细胞中的异常表达会影响肿瘤细胞的浸润及转移活性,说明Ezrin蛋白与肿瘤的发生、转移与预后密切相关。伴随着消化系统恶性肿瘤发病率的不断升高,严重影响到了人类的生活质量,探究Ezrin蛋白在肿瘤中的表达及其作用机制对于消化系统恶性肿瘤(如食管癌、结直肠癌、胃癌、肝癌、胰腺癌和胆道肿瘤)的早期诊断、治疗及预后评价等方面具有重要意义,同时也可为寻找新的基因治疗靶点及诊断用生物标志物提供新的依据。
引文
[1]YU Y,KHAN J,KHANNA C,et al.Expression profiling identifies the cytoskeletal organizer Ezrin and the developmental homeoprotein Six-1 as key metastatic regulators[J].Nat Med,2004,10(2):175-181.DOI:10.1038/nm966.
[2]KHANNA C,WAN X,BOSE S,et al.The membrane-cytoskeleton linker Ezrin is necessary for osteosarcoma metastasis[J].Nat Med,2004,10(2):182-186.DOI:10.1038/nm982.
[3]TACHIBANA K,HAGHPARAST S M,MIYAKE J.Inhibition of cell adhesion by phosphorylated Ezrin/Radixin/Moesin[J].Cell Adh Migr,2015,9(6):502-512.DOI:10.1080/19336918.2015.1113366.
[4]FEHON R G,MCCLATCHEY A I,BRETSCHER A.Organizing the cell cortex:the role of ERM proteins[J].Nat Rev Mol Cell Biol,2010,11(4):276-287.DOI:10.1038/nrm2866.
[5]GUNGOR-ORDUERI N E,TANG E I,CELIK-OZENCI C,et al.Ezrin is an actin binding protein that regulates sertoli cell and spermatid adhesion during spermatogenesis[J].Endocrinology,2014,155(10):3981-3995.DOI:10.1210/en.2014-1163.
[6]FIEVET B T,GAUTREAU A,ROY C,et al.Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of Ezrin[J].J Cell Biol,2004,164(5):653-659.DOI:10.1083/jcb.200307032.
[7]PUJUGUET P,DEL MAESTRO L,GAUTREAU A,et al.Ezrin regulates E-cadherin-dependent adherens junction assembly through Rac1 activation[J].Mol Biol Cell,2003,14(5):2181-2191.DOI:10.1091/mbc.E02-07-0410.
[8]KIM C,SHIN E,HONG S,et al.Clinical value of Ezrin expression in primary osteosarcoma[J].Cancer Res Treat,2009,41(3):138-144.DOI:10.4143/crt.2009.41.3.138.
[9]KRISHNAN K,BRUCE B,HEWITT S,et al.Ezrin mediates growth and survival in Ewing's sarcoma through the AKT/m TOR,but not the MAPK,signaling pathway[J].Clin Exp Metastasis,2006,23(3-4):227-236.DOI:10.1007/s10585-006-9033-y.
[10]HUANG X,XIAO D W,XU L Y,et al.Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma[J].Oncol Rep,2009,21(4):1123-1129.DOI:10.1369/jhc.5a6881.2006.
[11]SHEN Z Y,XU L Y,CHEN M H,et al.Upregulated expression of Ezrin and invasive phenotype in malignantly transformed esophageal epithelial cells[J].World J Gastroenterol,2003,9(6):1182-1186.DOI:10.3748/wjg.v9.i6.1182.
[12]ZHAO L P,HUANG L,TIAN X,et al.Knockdown of Ezrin suppresses the migration and angiogenesis of human umbilical vein endothelial cells in vitro[J].Huazhong Univ Sci Technolog Med Sci,2016,32(2):243-248.DOI:10.1007/s11596-016-1574-y.
[13]翟建文,杨晓刚,杨福申,等.Ezrin、E-cadherin在食管鳞癌中的表达及临床意义[J].癌症,2010,29(3):343-347.
[14]SHI R L,LI J F,QU Y,et al.Expression of Ezrin in gastric carcinoma and its significance[J].Chin J Gastrointest Surg,2006,9(5):433-435.
[15]苗杰,许欣,徐国萍,等.胃癌中Ezrin、MMP-14的表达及相关性[J].临床与实验病理学杂志,2014,30(6):614-618.
[16]ZHAO J,ZHANG X,XIN Y.Up-regulated expression of Ezrin and c-Met proteins are related to the metastasis and prognosis of gastric carcinomas[J].Histol Histopathol,2011,26(9):1111-1120.
[17]YANG L,GUO T,JIANG S,et al.Expression of Ezrin,HGF and c-Met and its clinicopathological significance in the benign and malignant lesions of the gallbladder[J].Hepatogastroenterology,2012,59(118):1769-1775.DOI:10.5754/hge11744.
[18]LI L,WANG Y Y,ZHAO Z S,et al.Ezrin is associated with gastric cancer progression and prognosis[J].Pathol Oncol Res,2011,17(4):909-915.DOI:10.1007/s12253-011-9402-y.
[19]CAO L L,XIE J W,LIN Y,et al.miR-183 inhibits invasion of gastric cancer by targeting Ezrin[J].Int J Clin Exp Pathol,2014,7(9):5582-5594.DOI:10.7314/apjcp.2014.15.16.6543.
[20]SHAN H G.Ezrin promotes invasion and metastasis of gastric cancer by up-regulating YAP protein expression[J].World Chin J Digestol,2015,23(23):3683-3686.DOI:10.11569/wcjd.v23.i23.3683.
[21]HISCOX S,JIANG W G.Ezrin regulates cell-cell and cell-matrix adhesion,a possible role with E-cadherin/beta-catenin[J].J Cell Sci,1999,112(Pt 18):3081-3090.
[22]王昕炜,丁小英,樊祥山,等.Ezrin和P53在结直肠癌中的表达及临床病理意义[J].现代医药卫生,2015,31(24):3689-3691,3693.DOI:10.3969/j.issn.1009-5519.2015.24.001.
[23]ATAMAN-NAL Y,BUSSERET S,CHARRIER J P,et al.Ezrin assay method for the in vitro diagnosis of colorectal cancer:U.S.Patent Application 14/701,002[P].2015-4-30.
[24]MARTN M,SIMON-ASSMANN P,KEDINGER M,et al.DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with Ezrin[J].Eur J Cell Biol,2006,85(8):769-783.DOI:10.1016/j.ejcb.2006.02.013.
[25]YU Y,KHAN J,KHANNA C,et al.Expression profiling identifies the cytoskeletal organizer Ezrin and the developmental homeoprotein Six-1 as key metastatic regulators[J].Nat Med,2004,10(2):175-181.DOI:10.1038/nm966.
[26]ABD-EL RAOUF S M,IBRAHIM T R,HEGAZY A A.Expression and significance of Ezrin and E-cadherin in colorectal carcinoma[J].Inter J Adv Res,2014,2(7):936-944.
[27]LEIPHRAKPAM P D,RAJPUT A,MATHIESEN M,et al.Ezrin expression and cell survival regulation in colorectal cancer[J].Cell Signal,2014,26(5):868-879.DOI:10.1016/j.cellsig.2014.01.014.
[28]申鹏,苏宁,陈斌,等.埃兹蛋白表达与肝细胞癌增殖及转移的关系研究[J].解放军医学杂志,2009,34(6):737-739.DOI:10.3321/j.issn:0577-7402.2009.06.025.
[29]ZHANG Y,HU M Y,WU W Z,et al.The membrane-cytoskeleton organizer Ezrin is necessary for hepatocellular carcinoma cell growth and invasiveness[J].J Cancer Res Clin Oncol,2006,132(11):685-697.DOI:10.1007/s00432-006-0117-5.
[30]BONILHA V L,RAYBORN M E,SAOTOME I,et al.Microvilli defects in retinas of Ezrin knockout mice[J].Exp Eye Res,2006,82(4):720-729.DOI:10.1016/j.exer.2005.09.013.
[31]KONG J,ZHOU X,HAN L,et al.Clinicopathological significance of Ezrin and SIX1 protein expression in alpha fetoproteinnegative hepatocellular carcinoma[J].Chin J Cell Mol Immunol,2016,32(2):236-239.
[32]CHEN Y,WANG D,GUO Z,et al.Rho kinase phosphorylation promotes Ezrin-mediated metastasis in hepatocellular carcinoma[J].Cancer Res,2011,71(5):1721-1729.DOI:10.1158/0008-5472.CAN-09-4683.
[33]OSADA S,SAJI S,KUNO T.Clinical significance of combination study of apoptotic factors and proliferating cell nuclear antigen in estimating the prognosis of hepatocellular carcinoma[J].J Surg Oncol,2004,85(1):48-54.DOI:10.1002/jso.20006.
[34]高飞,黄波,邹浩,等.紫杉醇化疗联合Ezrin-siRNA治疗转移性肝癌的实验研究[J].中华肝胆外科杂志,2014,20(2):133-136.DOI:10.3760/cma.j.issn.1007-8118.2014.02.014.
[35]SUN Y,WU J,CAI H,et al.A prospective study of autoantibodies to Ezrin and pancreatic cancer risk[J].Cancer Causes&Control,2016,27(6):831-835.DOI:10.1007/s10552-016-0757-y.
[36]MARTIN T A,HARRISON G,MANSEL R E,et al.The role of the CD44/Ezrin complex in cancer metastasis[J].Crit Rev Oncol Hematol,2003,46(2):165-186.DOI:10.1016/s1040-8428(02)00172-5.
[37]邹科见,周海兰,熊焰.胰腺癌中Ezrin蛋白和CD44v6蛋白的表达及其临床意义[J].中国普通外科杂志,2009,18(9):984-986.
[38]ZHANG J,DONG J,YANG Z,et al.Expression of Ezrin,CD44,and VEGF in giant cell tumor of bone and its significance[J].World J Surg Oncol,2015,13:168.DOI:10.1186/s12957-015-0579-5.
[39]孟云霄,于双妮,卢朝辉,等.RNA干扰Ezrin蛋白表达对胰腺癌细胞系Panc-1细胞生物学行为的影响[J].中华病理学杂志,2012,41(12):833-836.DOI:10.3760/cma.j.issn.0529-5807.2012.12.009.
[40]PIAO J,LIU S,XU Y,et al.Ezrin protein overexpression predicts the poor prognosis of pancreatic ductal adenocarcinomas[J].Exp Mol Pathol,2015,98(1):1-6.DOI:10.1016/j.yexmp.2014.11.003.
[41]GUEDJ N,VAQUERO J,CLAPRON A,et al.Loss of Ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E-cadherin[J].Histopathology,2016,69(2):211-221.DOI:10.1111/his.12931.
[42]王菲,孙学军,郑见宝,等.Ezrin蛋白在胆囊癌组织中的表达及其与血清CEA及CA19-9阳性率的关系[J].中国普外基础与临床杂志,2010,17(4):317-322.
[43]FAIS S,DE MILITO A,LOZUPONE F.The role of FAS to Ezrin association in FAS-mediated apoptosis[J].Apoptosis,2005,10(5):941-947.DOI:10.1007/s10495-005-0478-2.
[2]KHANNA C,WAN X,BOSE S,et al.The membrane-cytoskeleton linker Ezrin is necessary for osteosarcoma metastasis[J].Nat Med,2004,10(2):182-186.DOI:10.1038/nm982.
[3]TACHIBANA K,HAGHPARAST S M,MIYAKE J.Inhibition of cell adhesion by phosphorylated Ezrin/Radixin/Moesin[J].Cell Adh Migr,2015,9(6):502-512.DOI:10.1080/19336918.2015.1113366.
[4]FEHON R G,MCCLATCHEY A I,BRETSCHER A.Organizing the cell cortex:the role of ERM proteins[J].Nat Rev Mol Cell Biol,2010,11(4):276-287.DOI:10.1038/nrm2866.
[5]GUNGOR-ORDUERI N E,TANG E I,CELIK-OZENCI C,et al.Ezrin is an actin binding protein that regulates sertoli cell and spermatid adhesion during spermatogenesis[J].Endocrinology,2014,155(10):3981-3995.DOI:10.1210/en.2014-1163.
[6]FIEVET B T,GAUTREAU A,ROY C,et al.Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of Ezrin[J].J Cell Biol,2004,164(5):653-659.DOI:10.1083/jcb.200307032.
[7]PUJUGUET P,DEL MAESTRO L,GAUTREAU A,et al.Ezrin regulates E-cadherin-dependent adherens junction assembly through Rac1 activation[J].Mol Biol Cell,2003,14(5):2181-2191.DOI:10.1091/mbc.E02-07-0410.
[8]KIM C,SHIN E,HONG S,et al.Clinical value of Ezrin expression in primary osteosarcoma[J].Cancer Res Treat,2009,41(3):138-144.DOI:10.4143/crt.2009.41.3.138.
[9]KRISHNAN K,BRUCE B,HEWITT S,et al.Ezrin mediates growth and survival in Ewing's sarcoma through the AKT/m TOR,but not the MAPK,signaling pathway[J].Clin Exp Metastasis,2006,23(3-4):227-236.DOI:10.1007/s10585-006-9033-y.
[10]HUANG X,XIAO D W,XU L Y,et al.Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma[J].Oncol Rep,2009,21(4):1123-1129.DOI:10.1369/jhc.5a6881.2006.
[11]SHEN Z Y,XU L Y,CHEN M H,et al.Upregulated expression of Ezrin and invasive phenotype in malignantly transformed esophageal epithelial cells[J].World J Gastroenterol,2003,9(6):1182-1186.DOI:10.3748/wjg.v9.i6.1182.
[12]ZHAO L P,HUANG L,TIAN X,et al.Knockdown of Ezrin suppresses the migration and angiogenesis of human umbilical vein endothelial cells in vitro[J].Huazhong Univ Sci Technolog Med Sci,2016,32(2):243-248.DOI:10.1007/s11596-016-1574-y.
[13]翟建文,杨晓刚,杨福申,等.Ezrin、E-cadherin在食管鳞癌中的表达及临床意义[J].癌症,2010,29(3):343-347.
[14]SHI R L,LI J F,QU Y,et al.Expression of Ezrin in gastric carcinoma and its significance[J].Chin J Gastrointest Surg,2006,9(5):433-435.
[15]苗杰,许欣,徐国萍,等.胃癌中Ezrin、MMP-14的表达及相关性[J].临床与实验病理学杂志,2014,30(6):614-618.
[16]ZHAO J,ZHANG X,XIN Y.Up-regulated expression of Ezrin and c-Met proteins are related to the metastasis and prognosis of gastric carcinomas[J].Histol Histopathol,2011,26(9):1111-1120.
[17]YANG L,GUO T,JIANG S,et al.Expression of Ezrin,HGF and c-Met and its clinicopathological significance in the benign and malignant lesions of the gallbladder[J].Hepatogastroenterology,2012,59(118):1769-1775.DOI:10.5754/hge11744.
[18]LI L,WANG Y Y,ZHAO Z S,et al.Ezrin is associated with gastric cancer progression and prognosis[J].Pathol Oncol Res,2011,17(4):909-915.DOI:10.1007/s12253-011-9402-y.
[19]CAO L L,XIE J W,LIN Y,et al.miR-183 inhibits invasion of gastric cancer by targeting Ezrin[J].Int J Clin Exp Pathol,2014,7(9):5582-5594.DOI:10.7314/apjcp.2014.15.16.6543.
[20]SHAN H G.Ezrin promotes invasion and metastasis of gastric cancer by up-regulating YAP protein expression[J].World Chin J Digestol,2015,23(23):3683-3686.DOI:10.11569/wcjd.v23.i23.3683.
[21]HISCOX S,JIANG W G.Ezrin regulates cell-cell and cell-matrix adhesion,a possible role with E-cadherin/beta-catenin[J].J Cell Sci,1999,112(Pt 18):3081-3090.
[22]王昕炜,丁小英,樊祥山,等.Ezrin和P53在结直肠癌中的表达及临床病理意义[J].现代医药卫生,2015,31(24):3689-3691,3693.DOI:10.3969/j.issn.1009-5519.2015.24.001.
[23]ATAMAN-NAL Y,BUSSERET S,CHARRIER J P,et al.Ezrin assay method for the in vitro diagnosis of colorectal cancer:U.S.Patent Application 14/701,002[P].2015-4-30.
[24]MARTN M,SIMON-ASSMANN P,KEDINGER M,et al.DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with Ezrin[J].Eur J Cell Biol,2006,85(8):769-783.DOI:10.1016/j.ejcb.2006.02.013.
[25]YU Y,KHAN J,KHANNA C,et al.Expression profiling identifies the cytoskeletal organizer Ezrin and the developmental homeoprotein Six-1 as key metastatic regulators[J].Nat Med,2004,10(2):175-181.DOI:10.1038/nm966.
[26]ABD-EL RAOUF S M,IBRAHIM T R,HEGAZY A A.Expression and significance of Ezrin and E-cadherin in colorectal carcinoma[J].Inter J Adv Res,2014,2(7):936-944.
[27]LEIPHRAKPAM P D,RAJPUT A,MATHIESEN M,et al.Ezrin expression and cell survival regulation in colorectal cancer[J].Cell Signal,2014,26(5):868-879.DOI:10.1016/j.cellsig.2014.01.014.
[28]申鹏,苏宁,陈斌,等.埃兹蛋白表达与肝细胞癌增殖及转移的关系研究[J].解放军医学杂志,2009,34(6):737-739.DOI:10.3321/j.issn:0577-7402.2009.06.025.
[29]ZHANG Y,HU M Y,WU W Z,et al.The membrane-cytoskeleton organizer Ezrin is necessary for hepatocellular carcinoma cell growth and invasiveness[J].J Cancer Res Clin Oncol,2006,132(11):685-697.DOI:10.1007/s00432-006-0117-5.
[30]BONILHA V L,RAYBORN M E,SAOTOME I,et al.Microvilli defects in retinas of Ezrin knockout mice[J].Exp Eye Res,2006,82(4):720-729.DOI:10.1016/j.exer.2005.09.013.
[31]KONG J,ZHOU X,HAN L,et al.Clinicopathological significance of Ezrin and SIX1 protein expression in alpha fetoproteinnegative hepatocellular carcinoma[J].Chin J Cell Mol Immunol,2016,32(2):236-239.
[32]CHEN Y,WANG D,GUO Z,et al.Rho kinase phosphorylation promotes Ezrin-mediated metastasis in hepatocellular carcinoma[J].Cancer Res,2011,71(5):1721-1729.DOI:10.1158/0008-5472.CAN-09-4683.
[33]OSADA S,SAJI S,KUNO T.Clinical significance of combination study of apoptotic factors and proliferating cell nuclear antigen in estimating the prognosis of hepatocellular carcinoma[J].J Surg Oncol,2004,85(1):48-54.DOI:10.1002/jso.20006.
[34]高飞,黄波,邹浩,等.紫杉醇化疗联合Ezrin-siRNA治疗转移性肝癌的实验研究[J].中华肝胆外科杂志,2014,20(2):133-136.DOI:10.3760/cma.j.issn.1007-8118.2014.02.014.
[35]SUN Y,WU J,CAI H,et al.A prospective study of autoantibodies to Ezrin and pancreatic cancer risk[J].Cancer Causes&Control,2016,27(6):831-835.DOI:10.1007/s10552-016-0757-y.
[36]MARTIN T A,HARRISON G,MANSEL R E,et al.The role of the CD44/Ezrin complex in cancer metastasis[J].Crit Rev Oncol Hematol,2003,46(2):165-186.DOI:10.1016/s1040-8428(02)00172-5.
[37]邹科见,周海兰,熊焰.胰腺癌中Ezrin蛋白和CD44v6蛋白的表达及其临床意义[J].中国普通外科杂志,2009,18(9):984-986.
[38]ZHANG J,DONG J,YANG Z,et al.Expression of Ezrin,CD44,and VEGF in giant cell tumor of bone and its significance[J].World J Surg Oncol,2015,13:168.DOI:10.1186/s12957-015-0579-5.
[39]孟云霄,于双妮,卢朝辉,等.RNA干扰Ezrin蛋白表达对胰腺癌细胞系Panc-1细胞生物学行为的影响[J].中华病理学杂志,2012,41(12):833-836.DOI:10.3760/cma.j.issn.0529-5807.2012.12.009.
[40]PIAO J,LIU S,XU Y,et al.Ezrin protein overexpression predicts the poor prognosis of pancreatic ductal adenocarcinomas[J].Exp Mol Pathol,2015,98(1):1-6.DOI:10.1016/j.yexmp.2014.11.003.
[41]GUEDJ N,VAQUERO J,CLAPRON A,et al.Loss of Ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E-cadherin[J].Histopathology,2016,69(2):211-221.DOI:10.1111/his.12931.
[42]王菲,孙学军,郑见宝,等.Ezrin蛋白在胆囊癌组织中的表达及其与血清CEA及CA19-9阳性率的关系[J].中国普外基础与临床杂志,2010,17(4):317-322.
[43]FAIS S,DE MILITO A,LOZUPONE F.The role of FAS to Ezrin association in FAS-mediated apoptosis[J].Apoptosis,2005,10(5):941-947.DOI:10.1007/s10495-005-0478-2.