Wnt/β-catenin信号通路调控Sp5机制的研究进展
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摘要
Wnt/β-catenin信号通路是一条广泛存在于生物体内且在进化上具有高度保守特性的通路。该通路在细胞生长、发育、迁移及凋亡过程中发挥着重要作用。特异性蛋白-5(Sp5)作为Wnt/β-catenin信号通路的下游靶点,在发育过程中也有着重要的调控作用,包括细胞分化、组织形成及肿瘤的发生等。本文就Wnt/β-catenin信号通路对其下游分子Sp5的作用进行综述,明确Wnt/β-catenin-Sp5在疾病发展中的作用。
Wnt/β-catenin signaling pathway is a widely existing and highly conserved evolutionary pathway in organisms. This pathway plays an important role in cell growth, development, migration and apoptosis. Specificity protein-5(Sp5), as a downstream target of Wnt/β-catenin signaling pathway, also plays an important regulatory role in the development process, including cell differentiation, tissue formation and tumorigenesis. Starting from the Wnt/β-catenin signaling pathway, this paper reviews the role of Wnt/β-catenin-Sp5 in the development of the disease by reviewing its role in the downstream molecule Sp5.
Wnt/β-catenin signaling pathway is a widely existing and highly conserved evolutionary pathway in organisms. This pathway plays an important role in cell growth, development, migration and apoptosis. Specificity protein-5(Sp5), as a downstream target of Wnt/β-catenin signaling pathway, also plays an important regulatory role in the development process, including cell differentiation, tissue formation and tumorigenesis. Starting from the Wnt/β-catenin signaling pathway, this paper reviews the role of Wnt/β-catenin-Sp5 in the development of the disease by reviewing its role in the downstream molecule Sp5.
引文
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[3]Anastas JN,Moon RT.WNT signalling pathways as therapeutic targets in cancer[J].Nat Rev Cancer,2013,13(1):11-26.doi:10.1038/nrc3419.
[4]Waaler J,Machon O,von Kries JP,et al.Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth[J].Cancer Res,2011,71(1):197-205.doi:10.1158/0008-5472.CAN-10-1282.
[5]Ohtsuka S,Nakai-Futatsugi Y,Niwa H.LIF signal in mouse embryonic stem cells[J].JAKSTAT,2015,4(2):e1086520.doi:10.1080/21623996.2015.1086520.
[6]Tang L,Wang M,Liu D,et al.Sp5 induces the expression of Nanog to maintain mouse embryonic stem cell self-renewal[J].PLoS One,2017,12(9):e0185714.doi:10.1371/journal.pone.0185714.
[7]Ye S,Zhang D,Cheng F,et al.Wnt/β-catenin and LIF-Stat3signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal[J].J Cell Sci,2016,129(2):269-276.doi:10.1242/jcs.177675.
[8]汤玲.Sp5维持小鼠胚胎干细胞自我更新的分子机制研究[D].合肥:安徽大学,2018.Tang L.Molecular mechanisms of Sp5maintaining self-renewal of mouse embryonic stem cells[D].Hefei:Anhui University,2018.
[9]Dailey SC,Kozmikova I,Somorjai IML.Amphioxus Sp5 is a member of a conserved Specificity Protein complement and is modulated by Wnt/β-catenin signalling[J].Int J Dev Biol,2017,61(10/11/12):723-732.doi:10.1387/ijdb.170205is.
[10]Huggins IJ,Bos T,Gaylord O,et al.The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells[J].Nat Commun,2017,8(1):1034.doi:10.1038/s41467-017-01203-1.
[11]Weidinger G,Thorpe CJ,Wuennenberg-Stapleton K,et al.The Sp1-related transcription factors sp5 and sp5-like act downstream of Wnt/beta-catenin signaling in mesoderm and neuroectoderm patterning[J].Curr Biol,2005,15(6):489-500.doi:10.1016/j.cub.2005.01.041.
[12]Dunty WC Jr,Kennedy MWL,Chalamalasetty RB,et al.Transcriptional profiling of Wnt3a mutants identifies Sp transcription factors as essential effectors of the Wnt/β-catenin pathway in neuromesodermal stem cells[J].PLoS One,2014,9(1):e87018.doi:10.1371/journal.pone.0087018.
[13]Fujimura N,Vacik T,Machon O,et al.Wnt-mediated downregulation of Sp1 target genes by a transcriptional repressor Sp5[J].J Biol Chem,2007,282(2):1225-1237.doi:10.1074/jbc.M605851200.
[14]Monsoro-Burq AH,Wang E,Harland R.Msx1 and Pax3 cooperate to mediate FGF8 and WNT signals during Xenopus neural crest induction[J].Dev Cell,2005,8(2):167-178.doi:10.1016/j.devcel.2004.12.017.
[15]Park DS,Seo JH,Hong M,et al.Role of Sp5 as an essential early regulator of neural crest specification in xenopus[J].Dev Dyn,2013,242(12):1382-1394.doi:10.1002/dvdy.24034.
[16]Devotta A,Hong CS,Saint-Jeannet JP.Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3βindependent manner[J].Elife,2018,7.pii:e34404.doi:10.7554/eLife.34404.
[17]Treichel D,Becker MB,Gruss P.The novel transcription factor gene Sp5 exhibits a dynamic and highly restricted expression pattern during mouse embryogenesis[J].Mech Dev,2001,101(1/2):175-179.doi:10.1016/S0925-4773(00)00544-X.
[18]Bush JO,Jiang R.Palatogenesis:morphogenetic and molecular mechanisms of secondary palate development[J].Development,2012,139(2):231-243.doi:10.1242/dev.067082.
[19]宋庆高,陈尚,王芳,等.孕鼠锌摄入与外界不良因素共同作用对子代腭裂发生的影响[J].实用口腔医学杂志,2013,29(6):795-798.Song QG,Chen S,Wang F,et al.The effect of zinc of mother intaking and environmental factors on the incidence of fetus cleft palate of mice[J].J Pract Stomatol,2013,29(6):795-798.
[20]李泓运,宋庆高.锌对腭突融合期细胞凋亡的影响及与腭裂SP家族候选基因研究[D].遵义:遵义医学院,2018.Li HY,Song QG.The influence of zinc on apoptosis of palatal process fusion and the study of Sp family candidate gene based on cleft palate[D].Zunyi:Zunyi Medical College,2018.
[21]李欣蔚,宋庆高.不同锌离子浓度对腭突融合期细胞增殖影响及Sp家族表达分析[D].遵义:遵义医学院,2018.Li XW,Song QG.Effect of different concentration of zinc on palatal cell proliferation during palatine process fusion and expression analysis of Sp family[D].Zunyi:Zunyi Medical College,2018.
[22]Menezes R,Letra A,Kim AH,et al.Studies with Wnt genes and nonsyndromic cleft lip and palate[J].Birth Defects Res A Clin Mol Teratol,2010,88(11):995-1000.doi:10.1002/bdra.20720.
[23]Vijayan V,Ummer R,Weber R,et al.Association of WNT pathway genes with nonsyndromic cleft lip with or without cleft palate[J].Cleft Palate Craniofac J,2018,55(3):335-341.doi:10.1177/1055665617732782.
[24]Takahashi M,Nakamura Y,Obama K,et al.Identification of SP5 as a downstream gene of the beta-catenin/Tcf pathway and its enhanced expression in human colon cancer[J].Int J Oncol,2005,27(6):1483-1487.
[25]Herbst A,Jurinovic V,Krebs S,et al.Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling[J].BMC Genomics,2014,15:74.doi:10.1186/1471-2164-15-74.
[26]Miyamoto M,Hayashi T,Kawasaki Y,et al.Sp5 negatively regulates the proliferation of HCT116 cells by upregulating the transcription of p27[J].Oncol Lett,2018,15(3):4005-4009.doi:10.3892/ol.2018.7793.
[27]Fancy SP,Harrington EP,Baranzini SE,et al.Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer[J].Nat Neurosci,2014,17(4):506-512.doi:10.1038/nn.3676.
[28]Mologni L,Dekhil H,Ceccon M,et al.Colorectal tumors are effectively eradicated by combined inhibition of{beta}-catenin,KRAS,and the oncogenic transcription factor ITF2[J].Cancer Res,2010,70(18):7253-7263.doi:10.1158/0008-5472.CAN-10-1108.
[29]Muhammad BA,Almozyan S,Babaei-Jadidi R,et al.FLYWCH1,a novel suppressor of nuclearβ-catenin,regulates migration and morphology in colorectal cancer[J].Mol Cancer Res,2018,16(12):1977-1990.doi:10.1158/1541-7786.MCR-18-0262.
[30]Yong X,Tang B,Xiao YF,et al.Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer[J].Cancer Lett,2016,374(2):292-303.doi:10.1016/j.canlet.2016.02.032.
[31]Zhang M,Linghu E,Zhan Q,et al.Methylation of DACT2accelerates esophageal cancer development by activating Wnt signaling[J].Oncotarget,2016,7(14):17957-17969.doi:10.18632/oncotarget.7647.
[32]Chen J,Rajasekaran M,Xia H,et al.The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/β-catenin signalling pathway[J].Gut,2016,65(9):1522-1534.doi:10.1136/gutjnl-2015-310625.
[33]Evason KJ,Francisco MT,Juric V,et al.Identification of chemical inhibitors ofβ-catenin-driven liver tumorigenesis in zebrafish[J].PLoS Genet,2015,11(7):e1005305.doi:10.1371/journal.pgen.1005305.
[34]Chen Y,Guo Y,Ge X,et al.Elevated expression and potential roles of human Sp5,a member of Sp transcription factor family,in human cancers[J].Biochem Biophys Res Commun,2006,340(3):758-766.doi:10.1016/j.bbrc.2005.12.068.
[35]Hoverter NP,Ting JH,Sundaresh S,et al.A WNT/p21 circuit directed by the C-clamp,a sequence-specific DNA binding domain in TCFs[J].Mol Cell Biol,2012,32(18):3648-3662.doi:10.1128/MCB.06769-11.
[36]Khramtsov AI,Khramtsova GF,Tretiakova M,et al.Wnt/betacatenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome[J].Am J Pathol,2010,176(6):2911-2920.doi:10.2353/ajpath.2010.091125.
[37]Lamb R,Ablett MP,Spence K,et al.Wnt pathway activity in breast cancer sub-types and stem-like cells[J].PLoS One,2013,8(7):e67811.doi:10.1371/journal.pone.0067811.
[38]张玉梅,燕秋.黄芩苷上调FUT4表达及促进胚胎着床机制的研究[D].大连:大连医科大学,2015.Zhang YM,Yan Q.Study on Up-regulation of FUT4 expression by baicalin and promoting embryo implantation mechanism[D].Dalian:Dalian Medical University,2015.
[2]Kennedy MW,Chalamalasetty RB,Thomas S,et al.Sp5 and Sp8recruitβ-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription[J].Proc Natl Acad Sci U S A,2016,113(13):3545-3550.doi:10.1073/pnas.1519994113.
[3]Anastas JN,Moon RT.WNT signalling pathways as therapeutic targets in cancer[J].Nat Rev Cancer,2013,13(1):11-26.doi:10.1038/nrc3419.
[4]Waaler J,Machon O,von Kries JP,et al.Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth[J].Cancer Res,2011,71(1):197-205.doi:10.1158/0008-5472.CAN-10-1282.
[5]Ohtsuka S,Nakai-Futatsugi Y,Niwa H.LIF signal in mouse embryonic stem cells[J].JAKSTAT,2015,4(2):e1086520.doi:10.1080/21623996.2015.1086520.
[6]Tang L,Wang M,Liu D,et al.Sp5 induces the expression of Nanog to maintain mouse embryonic stem cell self-renewal[J].PLoS One,2017,12(9):e0185714.doi:10.1371/journal.pone.0185714.
[7]Ye S,Zhang D,Cheng F,et al.Wnt/β-catenin and LIF-Stat3signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal[J].J Cell Sci,2016,129(2):269-276.doi:10.1242/jcs.177675.
[8]汤玲.Sp5维持小鼠胚胎干细胞自我更新的分子机制研究[D].合肥:安徽大学,2018.Tang L.Molecular mechanisms of Sp5maintaining self-renewal of mouse embryonic stem cells[D].Hefei:Anhui University,2018.
[9]Dailey SC,Kozmikova I,Somorjai IML.Amphioxus Sp5 is a member of a conserved Specificity Protein complement and is modulated by Wnt/β-catenin signalling[J].Int J Dev Biol,2017,61(10/11/12):723-732.doi:10.1387/ijdb.170205is.
[10]Huggins IJ,Bos T,Gaylord O,et al.The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells[J].Nat Commun,2017,8(1):1034.doi:10.1038/s41467-017-01203-1.
[11]Weidinger G,Thorpe CJ,Wuennenberg-Stapleton K,et al.The Sp1-related transcription factors sp5 and sp5-like act downstream of Wnt/beta-catenin signaling in mesoderm and neuroectoderm patterning[J].Curr Biol,2005,15(6):489-500.doi:10.1016/j.cub.2005.01.041.
[12]Dunty WC Jr,Kennedy MWL,Chalamalasetty RB,et al.Transcriptional profiling of Wnt3a mutants identifies Sp transcription factors as essential effectors of the Wnt/β-catenin pathway in neuromesodermal stem cells[J].PLoS One,2014,9(1):e87018.doi:10.1371/journal.pone.0087018.
[13]Fujimura N,Vacik T,Machon O,et al.Wnt-mediated downregulation of Sp1 target genes by a transcriptional repressor Sp5[J].J Biol Chem,2007,282(2):1225-1237.doi:10.1074/jbc.M605851200.
[14]Monsoro-Burq AH,Wang E,Harland R.Msx1 and Pax3 cooperate to mediate FGF8 and WNT signals during Xenopus neural crest induction[J].Dev Cell,2005,8(2):167-178.doi:10.1016/j.devcel.2004.12.017.
[15]Park DS,Seo JH,Hong M,et al.Role of Sp5 as an essential early regulator of neural crest specification in xenopus[J].Dev Dyn,2013,242(12):1382-1394.doi:10.1002/dvdy.24034.
[16]Devotta A,Hong CS,Saint-Jeannet JP.Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3βindependent manner[J].Elife,2018,7.pii:e34404.doi:10.7554/eLife.34404.
[17]Treichel D,Becker MB,Gruss P.The novel transcription factor gene Sp5 exhibits a dynamic and highly restricted expression pattern during mouse embryogenesis[J].Mech Dev,2001,101(1/2):175-179.doi:10.1016/S0925-4773(00)00544-X.
[18]Bush JO,Jiang R.Palatogenesis:morphogenetic and molecular mechanisms of secondary palate development[J].Development,2012,139(2):231-243.doi:10.1242/dev.067082.
[19]宋庆高,陈尚,王芳,等.孕鼠锌摄入与外界不良因素共同作用对子代腭裂发生的影响[J].实用口腔医学杂志,2013,29(6):795-798.Song QG,Chen S,Wang F,et al.The effect of zinc of mother intaking and environmental factors on the incidence of fetus cleft palate of mice[J].J Pract Stomatol,2013,29(6):795-798.
[20]李泓运,宋庆高.锌对腭突融合期细胞凋亡的影响及与腭裂SP家族候选基因研究[D].遵义:遵义医学院,2018.Li HY,Song QG.The influence of zinc on apoptosis of palatal process fusion and the study of Sp family candidate gene based on cleft palate[D].Zunyi:Zunyi Medical College,2018.
[21]李欣蔚,宋庆高.不同锌离子浓度对腭突融合期细胞增殖影响及Sp家族表达分析[D].遵义:遵义医学院,2018.Li XW,Song QG.Effect of different concentration of zinc on palatal cell proliferation during palatine process fusion and expression analysis of Sp family[D].Zunyi:Zunyi Medical College,2018.
[22]Menezes R,Letra A,Kim AH,et al.Studies with Wnt genes and nonsyndromic cleft lip and palate[J].Birth Defects Res A Clin Mol Teratol,2010,88(11):995-1000.doi:10.1002/bdra.20720.
[23]Vijayan V,Ummer R,Weber R,et al.Association of WNT pathway genes with nonsyndromic cleft lip with or without cleft palate[J].Cleft Palate Craniofac J,2018,55(3):335-341.doi:10.1177/1055665617732782.
[24]Takahashi M,Nakamura Y,Obama K,et al.Identification of SP5 as a downstream gene of the beta-catenin/Tcf pathway and its enhanced expression in human colon cancer[J].Int J Oncol,2005,27(6):1483-1487.
[25]Herbst A,Jurinovic V,Krebs S,et al.Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling[J].BMC Genomics,2014,15:74.doi:10.1186/1471-2164-15-74.
[26]Miyamoto M,Hayashi T,Kawasaki Y,et al.Sp5 negatively regulates the proliferation of HCT116 cells by upregulating the transcription of p27[J].Oncol Lett,2018,15(3):4005-4009.doi:10.3892/ol.2018.7793.
[27]Fancy SP,Harrington EP,Baranzini SE,et al.Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer[J].Nat Neurosci,2014,17(4):506-512.doi:10.1038/nn.3676.
[28]Mologni L,Dekhil H,Ceccon M,et al.Colorectal tumors are effectively eradicated by combined inhibition of{beta}-catenin,KRAS,and the oncogenic transcription factor ITF2[J].Cancer Res,2010,70(18):7253-7263.doi:10.1158/0008-5472.CAN-10-1108.
[29]Muhammad BA,Almozyan S,Babaei-Jadidi R,et al.FLYWCH1,a novel suppressor of nuclearβ-catenin,regulates migration and morphology in colorectal cancer[J].Mol Cancer Res,2018,16(12):1977-1990.doi:10.1158/1541-7786.MCR-18-0262.
[30]Yong X,Tang B,Xiao YF,et al.Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer[J].Cancer Lett,2016,374(2):292-303.doi:10.1016/j.canlet.2016.02.032.
[31]Zhang M,Linghu E,Zhan Q,et al.Methylation of DACT2accelerates esophageal cancer development by activating Wnt signaling[J].Oncotarget,2016,7(14):17957-17969.doi:10.18632/oncotarget.7647.
[32]Chen J,Rajasekaran M,Xia H,et al.The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/β-catenin signalling pathway[J].Gut,2016,65(9):1522-1534.doi:10.1136/gutjnl-2015-310625.
[33]Evason KJ,Francisco MT,Juric V,et al.Identification of chemical inhibitors ofβ-catenin-driven liver tumorigenesis in zebrafish[J].PLoS Genet,2015,11(7):e1005305.doi:10.1371/journal.pgen.1005305.
[34]Chen Y,Guo Y,Ge X,et al.Elevated expression and potential roles of human Sp5,a member of Sp transcription factor family,in human cancers[J].Biochem Biophys Res Commun,2006,340(3):758-766.doi:10.1016/j.bbrc.2005.12.068.
[35]Hoverter NP,Ting JH,Sundaresh S,et al.A WNT/p21 circuit directed by the C-clamp,a sequence-specific DNA binding domain in TCFs[J].Mol Cell Biol,2012,32(18):3648-3662.doi:10.1128/MCB.06769-11.
[36]Khramtsov AI,Khramtsova GF,Tretiakova M,et al.Wnt/betacatenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome[J].Am J Pathol,2010,176(6):2911-2920.doi:10.2353/ajpath.2010.091125.
[37]Lamb R,Ablett MP,Spence K,et al.Wnt pathway activity in breast cancer sub-types and stem-like cells[J].PLoS One,2013,8(7):e67811.doi:10.1371/journal.pone.0067811.
[38]张玉梅,燕秋.黄芩苷上调FUT4表达及促进胚胎着床机制的研究[D].大连:大连医科大学,2015.Zhang YM,Yan Q.Study on Up-regulation of FUT4 expression by baicalin and promoting embryo implantation mechanism[D].Dalian:Dalian Medical University,2015.