Septin蛋白的生理功能及其对相关疾病发生发展的影响
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摘要
Septin属于GTP酶超级家族,是GTP结合蛋白,其在细胞中广泛表达,并被认为是第四种细胞骨架蛋白。Septin作为细胞支架蛋白可调控酵母出芽、细胞分裂等生理过程,并参与宿主细胞的防御反应。Septin的异常表达或突变与肿瘤和神经系统疾病的发生发展密切相关。该文就septin蛋白家族成员的上述生理功能、septin对肿瘤和神经系统疾病发生发展影响及septin在宿主免疫应答过程中的作用等方面进行研究进展的总结和展望。
Septins are GTP-binding proteins and belong to GTPase superfamily. Septins are ubiquitously expressed in cells and are recognized as the fourth component of the cytoskeleton. As a component of the cytoskeleton, septins are involved in many physiological and pathological processes, such as yeast budding, cell division and host immune response. The abnormal expression and mutation of septin are closely related to the development of cancers and nervous system diseases. In this review, we focus on the research progress of the physiological functions of septins, and discuss its effects on the occurrence and development of cancers and nervous system diseases, and summarizes the recent findings about the role of septins in host immune response.
Septins are GTP-binding proteins and belong to GTPase superfamily. Septins are ubiquitously expressed in cells and are recognized as the fourth component of the cytoskeleton. As a component of the cytoskeleton, septins are involved in many physiological and pathological processes, such as yeast budding, cell division and host immune response. The abnormal expression and mutation of septin are closely related to the development of cancers and nervous system diseases. In this review, we focus on the research progress of the physiological functions of septins, and discuss its effects on the occurrence and development of cancers and nervous system diseases, and summarizes the recent findings about the role of septins in host immune response.
引文
1 Hartwell LH.Genetic control of the cell division cycle in yeast.IV.Genes controlling bud emergence and cytokinesis.Exp Cell Res 1971;69(2):265-76.
2 Nakahira M,Macedo JN,Seraphim TV,Cavalcante N,Souza TA,Damalio JC,et al.A draft of the human septin interactome.PLoSOne 2010;5(11):e13799.
3 Mostowy S,Cossart P.Septins:the fourth component of the cytoskeleton.Nat Rev Mol Cell Biol 2012;13(3):183-94.
4 Macedo JN,Valadares NF,Marques IA,Ferreira FM,Damalio JC,Pereira HM,et al.The structure and properties of septin 3:a possible missing link in septin filament formation.Biochem J2013;450(1):95-105.
5 Zeraik AE,Pereira HM,Santos YV,Brand-Neto J,Spoerner M,Santos MS,et al.Crystal structure of a Schistosoma mansoni septin reveals the phenomenon of strand slippage in septins dependent on the nature of the bound nucleotide.J Biol Chem2014;289(11):7799-811.
6 Cao L,Ding X,Yu W,Yang X,Shen S,Yu L.Phylogenetic and evolutionary analysis of the septin protein family in metazoan.FEBS Lett 2007;581(28):5526-32.
7 Pan F,Malmberg RL,Momany M.Analysis of septins across kingdoms reveals orthology and new motifs.BMC Evol Biol2007;7(1):103.
8 Zhang J1,Kong C,Xie H,McPherson PS,Grinstein S,Trimble WS.Phosphatidylinositol polyphosphate binding to the mammalian septin H5 is modulated by GTP.Curr Biol 1999;9(24):1458-67.
9 Sala FA,Valadares NF,Macedo JNA,Borges JC,Garratt RC.Heterotypic coiled-coil formation is essential for the correct assembly of the septin heterofilament.Biophys J 2016;111(12):2608-19.
10 Estey MP,Kim MS,Trimble WS.Septins.Curr Biol 2011;21(10):R384-7.
11 Sellin ME,Sandblad L,Stenmark S,Gullberg M.Deciphering the rules governing assembly order of mammalian septin complexes.Mol Biol Cell 2011;22(17):3152-64.
12 Valadares NF,d’Muniz Pereira H,Ulian Araujo AP,Garratt RC.Septin structure and filament assembly.Biophys Rev 2017;9(5):481-500.
13 Neubauer K,Zieger B.The mammalian septin interactome.Front Cell Dev Biol 2017;5:1-9.
14 Bertin A1,McMurray MA,Grob P,Park SS,Garcia G,Patanwala I,et al.Saccharomyces cerevisiae septins:supramolecular organization of heterooligomers and the mechanism of filament assembly.Proc Natl Acad Sci USA 2008;105(24):8274-9.
15 Sirajuddin M,Farkasovsky M,Hauer F,Kühlmann D,Macara IG,Weyand M,et al.Structural insight into filament formation by mammalian septins.Nature 2007;449(7160):311-5.
16 Sirajuddin M,Farkasovsky M,Zent E,Wittinghofer A.GTPinduced conformational changes in septins and implications for function.Proc Natl Acad Sci USA 2009;106(39):16592-7.
17 Zent E,Vetter I,Wittinghofer A.Structural and biochemical properties of Sept7,a unique septin required for filament formation.Biol Chem 2011;392(8/9):791-7.
18 Torraca V,Mostowy S.Septins and Bacterial Infection.Front Cell Dev Biol 2016;4:127.
19 Okada S,Leda M,Hanna J,Savage NS,Bi E,Goryachev AB.Daughter cell identity emerges from the interplay of Cdc42,septins,and exocytosis.Dev Cell 2013;26(2):148-61.
20 Ong K,Wloka C,Okada S,Svitkina T,Bi E.Architecture and dynamic remodelling of the septin cytoskeleton during the cell cycle.Nat Commun 2014;5:5698.
21 Wloka C,Bi E.Mechanisms of cytokinesis in budding yeast.Cytoskeleton(Hoboken)2012;69(10):710-26.
22 Schneider C,Grois J,Renz C,Gronemeyer T,Johnsson N.Septin rings act as a template for myosin higher-order structures and inhibit redundant polarity establishment.J Cell Sci 2013;126(Pt15):3390-400.
23 Glomb O,Gronemeyer T.Septin organization and functions in budding yeast.Front Cell Dev Biol 2016;4:1-6.
24 Spiliotis ET,Kinoshita M,Nelson WJ.A mitotic septin scaffold required for mammalian chromosome congression and segregation.Science 2005;307(5716):1781-5.
25 Zhu M,Wang F,Yan F,Yao PY,Du J,Gao X et al.Septin 7Interacts with centromere-associated protein E and is required for its kinetochore localization.J Biol Chem 2008;283(27):18916-25.
26 Spiliotis ET.Spatial effects-site-specific regulation of actin and microtubule organization by septin GTPases.J Cell Sci 2018;doi:10.1242/jcs.207555.
27 Fujishima K,Kiyonari H,Kurisu J,Hirano T,Kengaku M.Targeted disruption of Sept3,a heteromeric assembly partner of Sept5 and Sept7 in axons,has no effect on developing CNSneurons.J Neurochem 2007;102(1):77-92.
28 Kremer BE,Haystead T,Macara IG.Mammalian septins regulate microtubule stability through interaction with the microtubulebinding protein MAP4.Mol Biol Cell 2005;16(10):4648-59.
29 Spiliotis ET,Hunt SJ,Hu Q,Kinoshita M,Nelson WJ.Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules.J Cell Biol 2008;180(2):295-303.
30 Amir S,Mabjeesh NJ.SEPT9_V1 protein expression is associated with human cancer cell resistance to microtubuledisrupting agents.Cancer Biol Ther 2007;6(12):1926-31.
31 Hu Q,Nelson WJ,Spiliotis ET.Forchlorfenuron alters mammalian septin assembly,organization,and dynamics.J Biol Chem 2008;283(43):29563-71.
32 Bowen JR1,Hwang D,Bai X,Roy D,Spiliotis ET.Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia.J Cell Biol 2011;194(2):187-97.
33 Lassen LB,Füchtbauer A,Schmitz A,S鴕ensen AB,Pedersen FS,Füchtbauer EM.Septin9 is involved in T-cell development and CD8+T-cell homeostasis.Cell Tissue Res 2013;352(3):695-705.
34 Senger K,Marka G,Soller K,Sakk V,Florian MC,Geiger H.Septin 6 regulates engraftment and lymphoid differentiation potential of murine long-term hematopoietic stem cells.Exp Hematol 2017;55:45-55.
35 Mujal AM,Gilden JK,Gérard A,Kinoshita M,Krummel MF.A septin requirement differentiates autonomous and contactfacilitated T cell proliferation.Nat Immunol 2016;17(3):315-22.
36 Mostowy S,Shenoy AR.The cytoskeleton in cell-autonomous immunity:structural determinants of host defence.Nat Rev Immunol 2015;15(9):559-73.
37 Croxen MA,Law RJ,Scholz R,Keeney KM,Wlodarska M,Finlay BB.Recent advances in understanding enteric pathogenic Escherichia coli.Clin Microbiol Rev 2013;26(4):822-80.
38 Scholz R,Imami K,Scott NE,Trimble WS,Foster LJ,Finlay BB.Novel host proteins and signaling pathways in enteropathogenic E.coli pathogenesis identified by global phosphoproteome analysis.Mol Cell Proteomics 2015;14(7):1927-45.
39 N鰈ke T,Schwan C,Lehmann F,豷tevold K,Pertz O,Aktories K.Septins guide microtubule protrusions induced by actindepolymerizing toxins like Clostridium difficile transferase(CDT).Proc Natl Acad Sci USA 2016;113(28):7870-5.
40 Kusumi A,Fujiwara TK,Chadda R,Xie M,Tsunoyama TA,Kalay Z,et al.Dynamic organizing principles of the plasma membrane that regulate signal transduction:commemorating the fortieth anniversary of Singer and Nicolson’s fluid-mosaic model.Annu Rev Cell Dev Biol 2012;28:215-50.
41 PizarrocerdáJ,Kühbacher A,Cossart P.Entry of Listeria monocytogenes in mammalian epithelial cells:an updated view.Cold Spring Harb Perspect Med 2012;2(11):705-9.
42 Kühbacher A,Emmenlauer M,R鋗o P,Kafai N,Dehio C,Cossart P,et al.Genome-wide siRNA screen identifies complementary signaling pathways involved in listeria infection and reveals different actin nucleation mechanisms during listeria sell invasion and actin comet tail formation.MBio 2015;6(3):e00598-15.
43 Weiner A,Mellouk N,Lopez-Montero N,Chang YY,Souque C,Schmitt C,et al.Macropinosomes are key players in early shigella invasion and vacuolar escape in epithelial cells.PLoSPathog 2016;12(5):e1005602.
44 Ray K,Marteyn B,Sansonetti PJ,Tang CM.Life on the inside:the intracellular lifestyle of cytosolic bacteria.Nat Rev Microbiol2009;7(5):333-40.
45 Kumar Y,Valdivia RH.Actin and intermediate filaments stabilize the Chlamydia trachomatis vacuole by forming dynamic structural scaffolds.Cell Host Microbe 2008;4(2):159-69.
46 Mostowy S,Bonazzi M,Hamon MA,Tham TN,Mallet A,Lelek M,et al.Entrapment of intracytosolic bacteria by septin cagelike structures.Cell Host Microbe 2010;8(5):433-44.
47 Connolly D,Abdesselam I,Verdier-Pinard P,Montagna C.Septin roles in tumorigenesis.Biol Chem 2011;392(8-9):725-38.
48 Megonigal MD,Rappaport EF,Jones DH,Williams TM,Lovett BD,Kelly KM,et al.In acute myeloid leukemia of infant twins fuses MLL with hCDCrel,a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.Proc Natl Acad Sci USA 1998;95(11):6413-8.
49 Osaka M,Rowley JD,Zeleznik-Le NJ.MSF(MLL septin-like fusion),a fusion partner gene of MLL,in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25).Proc Natl Acad Sci USA 1999;96(11):6428-33.
50 Cerveira N,Bizarro S,Teixeira MR.MLL-SEPTIN gene fusions in hematological malignancies.Biol Chem 2011;392(8/9):713-24.
51 Sellin ME,Holmfeldt P,Stenmark S,Gullberg M.Microtubules support a disk-like septin arrangement at the plasma membrane of mammalian cells.Mol Biol Cell 2011;22(23):4588-601.
52 S鴕ensen AB,Lund AH,Ethelberg S,Copeland NG,Jenkins NA,Pedersen FS.Sint1,a common integration site in SL3-3-induced T-cell lymphomas,Harbors a putative proto-oncogene with homology to the septin gene family.J Virol 2000;74(5):2161-8.
53 Montagna C,Lyu MS,Hunter K,Lukes L,Lowther W,Reppert T,et al.The Septin 9(MSF)gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines.Cancer Res 2003;63(9):2179-87.
54 McIlhatton MA,Burrows JF,Donaghy PG,Chanduloy S,Johnston PG,Russell SE.Genomic organization,complex splicing pattern and expression of a human septin gene on chromosome 17q25.3.Oncogene 2001;20(41):5930-9.
55 Chacko AD,Hyland PL,McDade SS,Hamilton PW,Russell SH,Hall PA.SEPT9_v4 expression induces morphological change,increased motility and disturbed polarity.J Pathol 2005;206(4):458-65.
56 Gonzalez ME,Makarova O,Peterson EA,Privette LM,Petty EM.Up-regulation of SEPT9_v1 stabilizes c-Jun-N-terminal kinase and contributes to its pro-proliferative activity in mammary epithelial cells.Cell Signal 2009;21(4):477-87.
57 Tóth K,Galamb O,Spisák S,Wichmann B,Sipos F,Valcz G,et al.The influence of methylated septin 9 gene on RNA and protein level in colorectal cancer.Pathol Oncol Res 2011;17(3):503-9.
58 Chen CH,Yan SL,Yang TH,Chen SF,Yeh YH,Ou JJ,et al.The relationship between the methylated septin-9 DNA blood test and stool occult blood test for diagnosing colorectal cancer in Taiwanese people.J Clin Lab Anal 2017;31(1):1-7.
59 Jemal A,Bray F,Center MM,Ferlay J,Ward E,Forman D.Global cancer statistics.CA Cancer J Clin 2011;61(2):69-90.
60 Lee J,Ou SH.Towards the goal of personalized medicine in gastric cancer-time to move beyond HER2 inhibition.Part I:Targeting receptor tyrosine kinase gene amplification.Discov Med 2013;15(85):333-41.
61 Roskoski R J.The ErbB/HER family of protein-tyrosine kinases and cancer.Pharmacol Res 2014;79:34-74.
62 Bang YJ,Van Cutsem E,Feyereislova A,Chung HC,Shen L,Sawaki A.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer(ToGA):a phase 3,open-label,randomised controlled trial.Lancet 2010;376(9742):687-97.
63 Gomez-Martín C,Lopez-Rios F,Aparicio J,Barriuso J,GarcíaCarbonero R,Pazo R,et al.A critical review of HER2-positive gastric cancer evaluation and treatment:from trastuzumab,and beyond.Cancer Lett 2014;351(1):30-40.
64 Arteaga CL,Sliwkowski MX,Osborne CK,Perez EA,Puglisi F,Gianni L.Treatment of HER2-positive breast cancer:current status and future perspectives.Nat Rev Clin Oncol 2011;9(1):16-32.
65 Bailey TA,Luan H,Clubb RJ,Naramura M,Band V,Raja SM,et al.Mechanisms of Trastuzumab resistance in ErbB2-driven breast cancer and newer opportunities to overcome therapy resistance.J Carcinog 2011;10:28.
66 Marcus EA,Tokhtaeva E,Turdikulova S,Capri J,Whitelegge JP,Scott DR2,et al.Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells.Biochem J2016;473(12):1703-18.
67 Ihara M,Tomimoto H,Kitayama H,Morioka Y,Akiguchi I,Shibasaki H,et al.Association of the cytoskeletal GTPbinding protein Sept4/H5 with cytoplasmic inclusions found in Parkinson’s disease and other synucleinopathies.J Biol Chem2003;278(26):24095-102.
68 Kurkinen KM,Marttinen M,Turner L,Natunen T,M鋕inen P,Haapalinna F,et al.SEPT8 modulatesβ-amyloidogenic processing of APP via affecting the sorting and accumulation of BACE1.J Cell Sci 2016;129(11):2224-38.
2 Nakahira M,Macedo JN,Seraphim TV,Cavalcante N,Souza TA,Damalio JC,et al.A draft of the human septin interactome.PLoSOne 2010;5(11):e13799.
3 Mostowy S,Cossart P.Septins:the fourth component of the cytoskeleton.Nat Rev Mol Cell Biol 2012;13(3):183-94.
4 Macedo JN,Valadares NF,Marques IA,Ferreira FM,Damalio JC,Pereira HM,et al.The structure and properties of septin 3:a possible missing link in septin filament formation.Biochem J2013;450(1):95-105.
5 Zeraik AE,Pereira HM,Santos YV,Brand-Neto J,Spoerner M,Santos MS,et al.Crystal structure of a Schistosoma mansoni septin reveals the phenomenon of strand slippage in septins dependent on the nature of the bound nucleotide.J Biol Chem2014;289(11):7799-811.
6 Cao L,Ding X,Yu W,Yang X,Shen S,Yu L.Phylogenetic and evolutionary analysis of the septin protein family in metazoan.FEBS Lett 2007;581(28):5526-32.
7 Pan F,Malmberg RL,Momany M.Analysis of septins across kingdoms reveals orthology and new motifs.BMC Evol Biol2007;7(1):103.
8 Zhang J1,Kong C,Xie H,McPherson PS,Grinstein S,Trimble WS.Phosphatidylinositol polyphosphate binding to the mammalian septin H5 is modulated by GTP.Curr Biol 1999;9(24):1458-67.
9 Sala FA,Valadares NF,Macedo JNA,Borges JC,Garratt RC.Heterotypic coiled-coil formation is essential for the correct assembly of the septin heterofilament.Biophys J 2016;111(12):2608-19.
10 Estey MP,Kim MS,Trimble WS.Septins.Curr Biol 2011;21(10):R384-7.
11 Sellin ME,Sandblad L,Stenmark S,Gullberg M.Deciphering the rules governing assembly order of mammalian septin complexes.Mol Biol Cell 2011;22(17):3152-64.
12 Valadares NF,d’Muniz Pereira H,Ulian Araujo AP,Garratt RC.Septin structure and filament assembly.Biophys Rev 2017;9(5):481-500.
13 Neubauer K,Zieger B.The mammalian septin interactome.Front Cell Dev Biol 2017;5:1-9.
14 Bertin A1,McMurray MA,Grob P,Park SS,Garcia G,Patanwala I,et al.Saccharomyces cerevisiae septins:supramolecular organization of heterooligomers and the mechanism of filament assembly.Proc Natl Acad Sci USA 2008;105(24):8274-9.
15 Sirajuddin M,Farkasovsky M,Hauer F,Kühlmann D,Macara IG,Weyand M,et al.Structural insight into filament formation by mammalian septins.Nature 2007;449(7160):311-5.
16 Sirajuddin M,Farkasovsky M,Zent E,Wittinghofer A.GTPinduced conformational changes in septins and implications for function.Proc Natl Acad Sci USA 2009;106(39):16592-7.
17 Zent E,Vetter I,Wittinghofer A.Structural and biochemical properties of Sept7,a unique septin required for filament formation.Biol Chem 2011;392(8/9):791-7.
18 Torraca V,Mostowy S.Septins and Bacterial Infection.Front Cell Dev Biol 2016;4:127.
19 Okada S,Leda M,Hanna J,Savage NS,Bi E,Goryachev AB.Daughter cell identity emerges from the interplay of Cdc42,septins,and exocytosis.Dev Cell 2013;26(2):148-61.
20 Ong K,Wloka C,Okada S,Svitkina T,Bi E.Architecture and dynamic remodelling of the septin cytoskeleton during the cell cycle.Nat Commun 2014;5:5698.
21 Wloka C,Bi E.Mechanisms of cytokinesis in budding yeast.Cytoskeleton(Hoboken)2012;69(10):710-26.
22 Schneider C,Grois J,Renz C,Gronemeyer T,Johnsson N.Septin rings act as a template for myosin higher-order structures and inhibit redundant polarity establishment.J Cell Sci 2013;126(Pt15):3390-400.
23 Glomb O,Gronemeyer T.Septin organization and functions in budding yeast.Front Cell Dev Biol 2016;4:1-6.
24 Spiliotis ET,Kinoshita M,Nelson WJ.A mitotic septin scaffold required for mammalian chromosome congression and segregation.Science 2005;307(5716):1781-5.
25 Zhu M,Wang F,Yan F,Yao PY,Du J,Gao X et al.Septin 7Interacts with centromere-associated protein E and is required for its kinetochore localization.J Biol Chem 2008;283(27):18916-25.
26 Spiliotis ET.Spatial effects-site-specific regulation of actin and microtubule organization by septin GTPases.J Cell Sci 2018;doi:10.1242/jcs.207555.
27 Fujishima K,Kiyonari H,Kurisu J,Hirano T,Kengaku M.Targeted disruption of Sept3,a heteromeric assembly partner of Sept5 and Sept7 in axons,has no effect on developing CNSneurons.J Neurochem 2007;102(1):77-92.
28 Kremer BE,Haystead T,Macara IG.Mammalian septins regulate microtubule stability through interaction with the microtubulebinding protein MAP4.Mol Biol Cell 2005;16(10):4648-59.
29 Spiliotis ET,Hunt SJ,Hu Q,Kinoshita M,Nelson WJ.Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules.J Cell Biol 2008;180(2):295-303.
30 Amir S,Mabjeesh NJ.SEPT9_V1 protein expression is associated with human cancer cell resistance to microtubuledisrupting agents.Cancer Biol Ther 2007;6(12):1926-31.
31 Hu Q,Nelson WJ,Spiliotis ET.Forchlorfenuron alters mammalian septin assembly,organization,and dynamics.J Biol Chem 2008;283(43):29563-71.
32 Bowen JR1,Hwang D,Bai X,Roy D,Spiliotis ET.Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia.J Cell Biol 2011;194(2):187-97.
33 Lassen LB,Füchtbauer A,Schmitz A,S鴕ensen AB,Pedersen FS,Füchtbauer EM.Septin9 is involved in T-cell development and CD8+T-cell homeostasis.Cell Tissue Res 2013;352(3):695-705.
34 Senger K,Marka G,Soller K,Sakk V,Florian MC,Geiger H.Septin 6 regulates engraftment and lymphoid differentiation potential of murine long-term hematopoietic stem cells.Exp Hematol 2017;55:45-55.
35 Mujal AM,Gilden JK,Gérard A,Kinoshita M,Krummel MF.A septin requirement differentiates autonomous and contactfacilitated T cell proliferation.Nat Immunol 2016;17(3):315-22.
36 Mostowy S,Shenoy AR.The cytoskeleton in cell-autonomous immunity:structural determinants of host defence.Nat Rev Immunol 2015;15(9):559-73.
37 Croxen MA,Law RJ,Scholz R,Keeney KM,Wlodarska M,Finlay BB.Recent advances in understanding enteric pathogenic Escherichia coli.Clin Microbiol Rev 2013;26(4):822-80.
38 Scholz R,Imami K,Scott NE,Trimble WS,Foster LJ,Finlay BB.Novel host proteins and signaling pathways in enteropathogenic E.coli pathogenesis identified by global phosphoproteome analysis.Mol Cell Proteomics 2015;14(7):1927-45.
39 N鰈ke T,Schwan C,Lehmann F,豷tevold K,Pertz O,Aktories K.Septins guide microtubule protrusions induced by actindepolymerizing toxins like Clostridium difficile transferase(CDT).Proc Natl Acad Sci USA 2016;113(28):7870-5.
40 Kusumi A,Fujiwara TK,Chadda R,Xie M,Tsunoyama TA,Kalay Z,et al.Dynamic organizing principles of the plasma membrane that regulate signal transduction:commemorating the fortieth anniversary of Singer and Nicolson’s fluid-mosaic model.Annu Rev Cell Dev Biol 2012;28:215-50.
41 PizarrocerdáJ,Kühbacher A,Cossart P.Entry of Listeria monocytogenes in mammalian epithelial cells:an updated view.Cold Spring Harb Perspect Med 2012;2(11):705-9.
42 Kühbacher A,Emmenlauer M,R鋗o P,Kafai N,Dehio C,Cossart P,et al.Genome-wide siRNA screen identifies complementary signaling pathways involved in listeria infection and reveals different actin nucleation mechanisms during listeria sell invasion and actin comet tail formation.MBio 2015;6(3):e00598-15.
43 Weiner A,Mellouk N,Lopez-Montero N,Chang YY,Souque C,Schmitt C,et al.Macropinosomes are key players in early shigella invasion and vacuolar escape in epithelial cells.PLoSPathog 2016;12(5):e1005602.
44 Ray K,Marteyn B,Sansonetti PJ,Tang CM.Life on the inside:the intracellular lifestyle of cytosolic bacteria.Nat Rev Microbiol2009;7(5):333-40.
45 Kumar Y,Valdivia RH.Actin and intermediate filaments stabilize the Chlamydia trachomatis vacuole by forming dynamic structural scaffolds.Cell Host Microbe 2008;4(2):159-69.
46 Mostowy S,Bonazzi M,Hamon MA,Tham TN,Mallet A,Lelek M,et al.Entrapment of intracytosolic bacteria by septin cagelike structures.Cell Host Microbe 2010;8(5):433-44.
47 Connolly D,Abdesselam I,Verdier-Pinard P,Montagna C.Septin roles in tumorigenesis.Biol Chem 2011;392(8-9):725-38.
48 Megonigal MD,Rappaport EF,Jones DH,Williams TM,Lovett BD,Kelly KM,et al.In acute myeloid leukemia of infant twins fuses MLL with hCDCrel,a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.Proc Natl Acad Sci USA 1998;95(11):6413-8.
49 Osaka M,Rowley JD,Zeleznik-Le NJ.MSF(MLL septin-like fusion),a fusion partner gene of MLL,in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25).Proc Natl Acad Sci USA 1999;96(11):6428-33.
50 Cerveira N,Bizarro S,Teixeira MR.MLL-SEPTIN gene fusions in hematological malignancies.Biol Chem 2011;392(8/9):713-24.
51 Sellin ME,Holmfeldt P,Stenmark S,Gullberg M.Microtubules support a disk-like septin arrangement at the plasma membrane of mammalian cells.Mol Biol Cell 2011;22(23):4588-601.
52 S鴕ensen AB,Lund AH,Ethelberg S,Copeland NG,Jenkins NA,Pedersen FS.Sint1,a common integration site in SL3-3-induced T-cell lymphomas,Harbors a putative proto-oncogene with homology to the septin gene family.J Virol 2000;74(5):2161-8.
53 Montagna C,Lyu MS,Hunter K,Lukes L,Lowther W,Reppert T,et al.The Septin 9(MSF)gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines.Cancer Res 2003;63(9):2179-87.
54 McIlhatton MA,Burrows JF,Donaghy PG,Chanduloy S,Johnston PG,Russell SE.Genomic organization,complex splicing pattern and expression of a human septin gene on chromosome 17q25.3.Oncogene 2001;20(41):5930-9.
55 Chacko AD,Hyland PL,McDade SS,Hamilton PW,Russell SH,Hall PA.SEPT9_v4 expression induces morphological change,increased motility and disturbed polarity.J Pathol 2005;206(4):458-65.
56 Gonzalez ME,Makarova O,Peterson EA,Privette LM,Petty EM.Up-regulation of SEPT9_v1 stabilizes c-Jun-N-terminal kinase and contributes to its pro-proliferative activity in mammary epithelial cells.Cell Signal 2009;21(4):477-87.
57 Tóth K,Galamb O,Spisák S,Wichmann B,Sipos F,Valcz G,et al.The influence of methylated septin 9 gene on RNA and protein level in colorectal cancer.Pathol Oncol Res 2011;17(3):503-9.
58 Chen CH,Yan SL,Yang TH,Chen SF,Yeh YH,Ou JJ,et al.The relationship between the methylated septin-9 DNA blood test and stool occult blood test for diagnosing colorectal cancer in Taiwanese people.J Clin Lab Anal 2017;31(1):1-7.
59 Jemal A,Bray F,Center MM,Ferlay J,Ward E,Forman D.Global cancer statistics.CA Cancer J Clin 2011;61(2):69-90.
60 Lee J,Ou SH.Towards the goal of personalized medicine in gastric cancer-time to move beyond HER2 inhibition.Part I:Targeting receptor tyrosine kinase gene amplification.Discov Med 2013;15(85):333-41.
61 Roskoski R J.The ErbB/HER family of protein-tyrosine kinases and cancer.Pharmacol Res 2014;79:34-74.
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