参考文献
[1]Furnari FB，Fenton T，Bachoo RM，et al.Malignant astrocytic glioma:genetics，biology，and paths to treatment.Genes＆development，2007，21(21):2683-2710.
[2]Partap S，Fisher PG.Update on new treatments and developments in childhood brain tumors.Current opinion in pediatrics，2007，19(6):670-674.
[3]Devriendt D.Treatment of brain metastases.Revue medicale de Bruxelles，2012，33(4):371-376.
[4]Tsao MN，Lloyd N，Wong RK，et al.Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.Cochrane Database Syst Rev，2012，4:CD003869.
[5]Grimm SA.Treatment of brain metastases:chemotherapy.Current oncology reports，2012，14(1):85-90.
[6]Kotliarova S，Fine HA.SnapShot:glioblastoma multiforme.Cancer cell，2012，21(5):710-710 e711.
[7]Foster R，Hu KQ，Lu Y，et al.Identification of a novel human Rho protein with unusual properties:GTPase deficiency and in vivo farnesylation.Molecular and cellular biology，1996，16(6):2689-2699.
[8]Jaffe AB，Hall A.Rho GTPases:biochemistry and biology.Annual review of cell and developmental biology，2005，21:247-269.
[9]Peris B，Gonzalez-Granero S，Ballester-Lurbe B，et al.Neuronal polarization is impaired in mice lacking RhoE expression.Journal of neurochemistry，2012，121(6):903-914.
[10]Chardin P.Function and regulation of Rnd proteins.Nature reviews Molecular cell biology，2006，7(1):54-62.
[11]Riento K，Villalonga P，Garg R，et al.Function and regulation of RhoE.Biochemical Society transactions，2005，33(Pt 4):649-651.
[12]Ma W，Wong CC，Tung EK，et al.RhoE is frequently down regulated in HCC and suppresses HCC invasion through antagonizing the Rho/ROCK/MYPT pathway.Hepatology，2012，57(1):152-161.
[13]Grise F，Sena S，Bidaud-Meynard A，et al.Rnd3/RhoE Is downregulated in hepatocellular carcinoma and controls cellular invasion.Hepatology，2012，55(6):1766-1775.
[14]Ma W，Wong CC，Tung EK，et al.RhoE is frequently downregulated in hepatocellular carcinoma(HCC)and suppresses HCC invasion through antagonizing the Rho/Rho-Kinase/Myosin phosphatase target pathway.Hepatology，2013，57(1):152-161.
[15]Zhou HJ，Li LL，Yue CX，et al.The effect of RhoE on CD44 promoter and the malignant behaviors of colorectal cancer cell.Sichuan da xue xue bao Yi xue ban＝Journal of Sichuan University Medical science edition，2011，42(5):589-593.
[16]Zhao H，Yang J，Fan T，et al.RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and modulates the PTEN/PI3K/Akt signaling pathway.Tumour biology:the journal of the International Society for Oncodevelopmental Biology and Medicine，2012，33(5):1363-1374.
[17]Klein RM，Aplin AE.Rnd3 regulation of the actin cytoskeleton promotes melanoma migration and invasive outgrowth in three dimensions.Cancer research，2009，69(6):2224-2233.
[18]Poch E，Minambres R，Mocholi E，et al.RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line.Experimental cell research，2007，313(4):719-731.
[19]Xi Lin BL，Xiangsheng Yang，Xiaojing Yue，et al.Genetic deletion of Rnd3 results in aqueductal stenosis leading to hydrocephalus through upregulation of Notch signaling.Proceedings of the National Academy of Sciences，2013，In press.
[20]Chen J，McKay RM，Parada LF.Malignant glioma:lessons from genomics，mouse models，and stem cells.Cell，2012，149(1):36-47.
[21]Purow BW，Haque RM，Noel MW，et al.Expression of Notch-1 and its ligands，Delta-like-1 and Jagged-1，is critical for glioma cell survival and proliferation.Cancer research，2005，65(6):2353-2363.
[22]Pang RT，Leung CO，Lee CL，et al.MicroRNA-34a is a tumor suppressor in choriocarcinoma via regulation of Delta-like1.BMC cancer，2013，13:25.
[23]Li XJ，Ji MH，Zhong SL，et al.MicroRNA-34a modulates chemosensitivity of breast cancer cells to adriamycin by targeting Notch1.Archives of medical research，2012，43(7):514-521.
[24]Zhang C，Yao Z，Zhu M，et al.Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting Notch1.Journal of Huazhong University of Science and Technology Medical sciences＝Hua zhong ke ji da xue xue bao Yi xue Ying De wen ban＝Huazhong keji daxue xuebao Yixue Yingdewen ban，2012，32(3):375-382.
[25]Yu X，Zhang W，Ning Q，et al.MicroRNA-34a inhibits human brain glioma cell growth by down-regulation of Notch1.Journal of Huazhong University of Science and Technology Medical sciences＝Hua zhong ke ji da xue xue bao Yi xue Ying De wen ban＝Huazhong keji daxue xuebao Yixue Yingdewen ban，2012，32(3):370-374.
[26]Du R，Sun W，Xia L，et al.Hypoxia-induced down-regulation ofmicroRNA-34a promotes EMT by targeting the Notch signaling pathway in tubular epithelial cells.PloS one，2012，7(2):e30771.
[27]Li WB，Ma MW，Dong LJ，et al.MicroRNA-34a targets notch1 and inhibits cell proliferation in glioblastoma multiforme.Cancer biology＆therapy，2011，12(6):477-483.
[28]Pang RT，Leung CO，Ye TM，et al.MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells.Carcinogenesis，2010，31(6):1037-1044.
[29]Li Y，Guessous F，Zhang Y，et al.MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes.Cancer research，2009，69(19):7569-7576.
[30]Bai Y，Qian C，Qian L，et al.Integrin CD11b negatively regulates TLR9-triggered dendritic cell cross-priming by upregulating microRNA-146a.J Immunol，2012，188(11):5293-5302.
[31]Croft DR，Olson MF.Transcriptional regulation of Rho GTPase signaling.Transcription，2011，2(5):211-215.
[32]Pacary E，Heng J，Azzarelli R，et al.Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling.Neuron，2011，69(6):1069-1084.
[33]Ryan KR，Lock FE，Heath JK，et al.Plakoglobin-dependent regulation of keratinocyte apoptosis by Rnd3.Journal of cell science，2012，125(Pt 13):3202-3209.
[34]Luo H，Zou J，Dong Z，et al.Up-regulated miR-17 promotes cell proliferation，tumour growth and cell cycle progression by targeting the RND3 tumour suppressor gene in colorectal carcinoma.The Biochemical journal，2012，442(2):311-321.
[35]Quante M，Bhagat G，Abrams JA，et al.Bile acid andinflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia.Cancer cell，2012，21(1):36-51.
[36]Li D，Delaney JC，Page CM，et al.Exocyclic carbons adjacent to the N6 of adenine are targets for oxidation by the Escherichia coli adaptive response protein AlkB.Journal of the American Chemical Society，2012，134(21):8896-8901.
[37]Luo H，Dong Z，Zou J，et al.Down-regulation of RhoE is associated with progression and poor prognosis in hepatocellular carcinoma.Journal of surgical oncology，2012，105(7):699-704.
[38]Bektic J，Pfeil K，Berger AP，et al.Small G-protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis.The Prostate，2005，64(4):332-340.
[39]Belgiovine C，Frapolli R，Bonezzi K，et al.Reduced expression of the ROCK inhibitor Rnd3 is associated with increased invasiveness and metastatic potential in mesenchymal tumor cells.PloS one，2010，5(11):e14154.
[40]Katiyar P，Aplin AE.FOXD3 regulates migration properties and Rnd3 expression in melanoma cells.Molecular cancer research:MCR，2011，9(5):545-552.
[41]Barrett LE，Granot Z，Coker C，et al.Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma.Cancer cell，2012，21(1):11-24.
[42]Bruna A，Darken RS，Rojo F，et al.High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene.Cancer cell，2007，11(2):147-160.
[43]Komander D，Garg R，Wan PT，et al.Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure.The EMBO journal，2008，27(23):3175-3185.
[44]Riento K，Totty N，Villalonga P，et al.RhoE function isregulated by ROCK I-mediated phosphorylation.The EMBO journal，2005，24(6):1170-1180.
[45]Zhang C，Zhou F，Li N，et al.Overexpression of RhoE has a prognostic value in non-small cell lung cancer.Annals of surgical oncology，2007，14(9):2628-2635.
[46]Villalonga P，Guasch RM，Riento K，et al.RhoE inhibits cell cycle progression and Ras-induced transformation.Molecular and cellular biology，2004，24(18):7829-7840.
[47]Tzoneva G，Ferrando AA.Recent advances on NOTCH signaling in T-ALL.Current topics in microbiology and immunology，2012，360:163-182.
[48]Gridley T.Notch signaling in vascular development and physiology.Development，2007，134(15):2709-2718.
[49]Stockhausen MT，Kristoffersen K，Poulsen HS.Notch signaling and brain tumors.Advances in experimental medicine and biology，2012，727:289-304.
[50]Lino MM，Merlo A，Boulay JL.Notch signaling in glioblastoma:a developmental drug target?BMC medicine，2010，8:72.
[51]Jiang L，Wu J，Chen Q，et al.Notch1 expression is upregulated in glioma and is associated with tumor progression.Journal of clinical neuroscience:official journal of the Neurosurgical Society of Australasia，2011，18(3):387-390.
[52]Xu P，Pu PY，Kang CS，et al.[Differential expression of Notch1 and Notch2 in astrocytoma and medulloblastoma].Zhonghua bing li xue za zhi Chinese journal of pathology，2008，37(7):450-453.
[53]Engh JA.Notch1 identified as a prognostic factor for glioma patients.Neurosurgery，2011，68(6):N22-23.
[54]Li J，Cui Y，Gao G，et al.Notch1 is an independent prognostic factor for patients with glioma.Journal of surgical oncology，2011，103(8):813-817.
[55]Phillips HS，Kharbanda S，Chen R，et al.Molecular subclassesof high-grade glioma predict prognosis，delineate a pattern of disease progression，and resemble stages in neurogenesis.Cancer cell，2006，9(3):157-173.
[56]Chen J，Kesari S，Rooney C，et al.Inhibition of notch signaling blocks growth of glioblastoma cell lines and tumor neurospheres.Genes＆cancer，2010，1(8):822-835.
[57]Kopan R，Ilagan MX.The canonical Notch signaling pathway:unfolding the activation mechanism.Cell，2009，137(2):216-233.(https://www.daowen.com)
[58]Guruharsha KG，Kankel MW，Artavanis-Tsakonas S.The Notch signalling system:recent insights into the complexity of a conserved pathway.Nature reviews Genetics，2012，13(9):654-666.
[59]Mei J，Bachoo R，Zhang CL.MicroRNA-146a inhibits glioma development by targeting Notch1.Molecular and cellular biology，2011，31(17):3584-3592.
[60]Ying M，Sang Y，Li Y，et al.Kruppel-like family of transcription factor 9，a differentiation-associated transcription factor，suppresses Notch1 signaling and inhibits glioblastoma-initiating stem cells.Stem Cells，2011，29(1):20-31.
[61]Raghu H，Gondi CS，Dinh DH，et al.Specific knockdown of uPA/uPAR attenuates invasion in glioblastoma cells and xenografts by inhibition of cleavage and trafficking of Notch-1 receptor.Molecular cancer，2011，10:130.
[62]Takebe N，Harris PJ，Warren RQ，et al.Targeting cancer stem cells by inhibiting Wnt，Notch，and Hedgehog pathways.Nature reviews Clinical oncology，2011，8(2):97-106.
[63]Fouladi M，Stewart CF，Olson J，et al.Phase I trial of MK-0752 in children with refractory CNS malignancies:a pediatric brain tumor consortium study.Journal of clinical oncology:official journal of the American Society of Clinical Oncology，2011，29(26):3529-3534.
[64]Rocher-Ros V，Marco S，Mao JH，et al.Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7.Oncogene，2010，29(20):2950-2961.
[65]Jin YH，Kim H，Ki H，et al.Beta-catenin modulates the level and transcriptional activity of Notch1/NICD through its direct interaction.Biochimica et biophysica acta，2009，1793(2):290-299.
[66]O'Neil J，Grim J，Strack P，et al.FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gammasecretase inhibitors.The Journal of experimental medicine，2007，204(8):1813-1824.
[67]Wherlock M，Mellor H.The Rho GTPase family:a Racs to Wrchs story.Journal of cell science，2002，115(Pt 2):239-240.
[68]Philips A，Blein M，Robert A，et al.Ascidians as a vertebratelike model organism for physiological studies of Rho GTPase signaling.Biology of the cell/under the auspices of the European Cell Biology Organization，2003，95(5):295-302.
[69]Wunnenberg-Stapleton K，Blitz IL，Hashimoto C，et al.Involvement of the small GTPases XRhoA and XRnd1 in cell adhesion and head formation in early Xenopus development.Development，1999，126(23):5339-5351.
[70]Nobes CD，Lauritzen I，Mattei MG，et al.A new member of the Rho family，Rnd1，promotes disassembly of actin filament structures and loss of cell adhesion.The Journal of cell biology，1998，141(1):187-197.
[71]Fiegen D，Blumenstein L，Stege P，et al.Crystal structure of Rnd3/RhoE:functional implications.FEBS letters，2002，525(1-3):100-104.
[72]Garavini H，Riento K，Phelan JP，et al.Crystal structure of the core domain of RhoE/Rnd3:a constitutively activated small Gprotein.Biochemistry，2002，41(20):6303-6310.
[73]Riento K，Guasch RM，Garg R，et al.RhoE binds to ROCK I and inhibits downstream signaling.Molecular and cellular biology，2003，23(12):4219-4229.
[74]Zhou Y，Li S，Huang Q，et al.Nanog suppresses cell migration by downregulating thymosin beta4 and Rnd3.Journal of molecular cell biology，2013.
[75]Guasch RM，Scambler P，Jones GE，et al.RhoE regulates actin cytoskeleton organization and cell migration.Molecular and cellular biology，1998，18(8):4761-4771.
[76]Ishikawa Y，Katoh H，Negishi M.A role of Rnd1 GTPase in dendritic spine formation in hippocampal neurons.The Journal of neuroscience:the official journal of the Society for Neuroscience，2003，23(35):11065-11072.
[77]Wennerberg K，Forget MA，Ellerbroek SM，et al.Rnd proteins function as RhoA antagonists by activating p190 RhoGAP.Current biology:CB，2003，13(13):1106-1115.
[78]Vayssiere B，Zalcman G，Mahe Y，et al.Interaction of the Grb7 adapter protein with Rnd1，a new member of the Rho family.FEBS letters，2000，467(1):91-96.
[79]Han DC，Shen TL，Miao H，et al.EphB1 associates with Grb7 and regulates cell migration.The Journal of biological chemistry，2002，277(47):45655-45661.
[80]Nishi M，Takeshima H，Houtani T，et al.RhoN，a novel small GTP-binding protein expressed predominantly in neurons and hepatic stellate cells.Brain research Molecular brain research，1999，67(1):74-81.
[81]Fujita H，Katoh H，Ishikawa Y，et al.Rapostlin is a novel effector of Rnd2 GTPase inducing neurite branching.The Journal of biological chemistry，2002，277(47):45428-45434.
[82]Kakimoto T，Katoh H，Negishi M.Identification of splicingvariants of Rapostlin，a novel RND2 effector that interacts with neural Wiskott-Aldrich syndrome protein and induces neurite branching.The Journal of biological chemistry，2004，279(14):14104-14110.
[83]Katoh H，Harada A，Mori K，et al.Socius is a novel Rnd GTPase-interacting protein involved in disassembly of actin stress fibers.Molecular and cellular biology，2002，22(9):2952-2964.
[84]Naud N，Toure A，Liu J，et al.Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells.The Biochemical journal，2003，372(Pt 1):105-112.
[85]Yuce O，Piekny A，Glotzer M.An ECT2-centralspindlin complex regulates the localization and function of RhoA.The Journal of cell biology，2005，170(4):571-582.
[86]Hansen SH，Zegers MM，Woodrow M，et al.Induced expression of Rnd3 is associated with transformation of polarized epithelial cells by the Raf-MEK-extracellular signal-regulated kinase pathway.Molecular and cellular biology，2000，20(24):9364-9375.
[87]Xia W，Li J，Chen L，et al.MicroRNA-200b regulates cyclin D1 expression and promotes S-phase entry by targeting RND3 in HeLa cells.Molecular and cellular biochemistry，2010，344(1-2):261-266.
[88]Collett GP，Goh XF，Linton EA，et al.RhoE is regulated by cyclic AMP and promotes fusion of human BeWo choriocarcinoma cells.PloS one，2012，7(1):e30453.
[89]Zhou J，Li K，Gu Y，et al.Transcriptional up-regulation of RhoE by hypoxia-inducible factor(HIF)-1 promotes epithelial to mesenchymal transition of gastric cancer cells during hypoxia.Biochemical and biophysical research communications，2011，415(2):348-354.
[90]Murakami T，Fujimoto M，Ohtsuki M，et al.Expression profilingof cancer-related genes in human keratinocytes following non-lethal ultraviolet B irradiation.Journal of dermatological science，2001，27(2):121-129.
[91]Cario-Toumaniantz C，Reillaudoux G，Sauzeau V，et al.Modulation of RhoA-Rho kinase-mediated Ca2＋sensitization of rabbit myometrium during pregnancy-role of Rnd3.The Journal of physiology，2003，552(Pt 2):403-413.
[92]Kim YS，Kim B，Karaki H，et al.Up-regulation of Rnd1 during pregnancy serves as a negative-feedback control for Ca2＋sensitization of contractile elements in rat myometrium.Biochemical and biophysical research communications，2003，311(4):972-978.
[93]Loirand G，Cario-Toumaniantz C，Chardin P，et al.The Rhorelated protein Rnd1 inhibits Ca2＋sensitization of rat smooth muscle.The Journal of physiology，1999，516(Pt 3):825-834.
[94]Cario-Toumaniantz C，Evellin S，Maury S，et al.Role of Rho kinase signalling in healthy and varicose human saphenous veins.British journal of pharmacology，2002，137(2):205-212.
[95]Camerer E，Gjernes E，Wiiger M，et al.Binding of factor VIIa to tissue factor on keratinocytes induces gene expression.The Journal of biological chemistry，2000，275(9):6580-6585.
[96]Nishigaki M，Aoyagi K，Danjoh I，et al.Discovery of aberrant expression of R-RAS by cancer-linked DNA hypomethylation in gastric cancer using microarrays.Cancer research，2005，65(6):2115-2124.
[97]Warton K，Foster NC，Gold WA，et al.A novel gene family induced by acute inflammation in endothelial cells.Gene，2004，342(1):85-95.
[98]Jiang H，Van De Ven C，Satwani P，et al.Differential gene expression patterns by oligonucleotide microarray of basal versus lipopolysaccharide-activated monocytes from cord blood versus adultperipheral blood.J Immunol，2004，172(10):5870-5879.
[99]Chardin P.GTPase regulation:getting aRnd Rock and Rho inhibition.Current biology:CB，2003，13(18):R702-704.
[100]Riento K，Ridley AJ.Rocks:multifunctional kinases in cell behaviour.Nature reviews Molecular cell biology，2003，4(6):446-456.
[101]Sauzeau V，Le Jeune H，Cario-Toumaniantz C，et al.Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoAinduced Ca2＋sensitization of contraction in vascular smooth muscle.The Journal of biological chemistry，2000，275(28):21722-21729.
[102]Doye A，Mettouchi A，Bossis G，et al.CNF1 exploits the ubiquitin-proteasome machinery to restrict Rho GTPase activation for bacterial host cell invasion.Cell，2002，111(4):553-564.
[103]Wang HR，Zhang Y，Ozdamar B，et al.Regulation of cell polarity and protrusion formation by targeting RhoA for degradation.Science，2003，302(5651):1775-1779.
[104]Krugmann S，Williams R，Stephens L，et al.ARAP3 is a PI3Kand rap-regulated GAP for RhoA.Current biology:CB，2004，14(15):1380-1384.
[105]Rolli-Derkinderen M，Sauzeau V，Boyer L，et al.Phosphorylation of serine 188 protects RhoA from ubiquitin/proteasome-mediated degradation in vascular smooth muscle cells.Circulation research，2005，96(11):1152-1160.
[106]Riou P，Villalonga P，Ridley AJ.Rnd proteins:multifunctional regulators of the cytoskeleton and cell cycle progression.BioEssays:news and reviews in molecular，cellular and developmental biology，2010，32(11):986-992.
[107]Boswell SA，Ongusaha PP，Nghiem P，et al.The protective role of a small GTPase RhoE against UVB-induced DNA damage inkeratinocytes.The Journal of biological chemistry，2007，282(7):4850-4858.
[108]Nadiminty N，Dutt S，Tepper C，et al.Microarray analysis reveals potential target genes of NF-kappaB2/p52 in LNCaP prostate cancer cells.The Prostate，2010，70(3):276-287.
[109]Gress TM，Muller-Pillasch F，Geng M，et al.A pancreatic cancer-specific expression profile.Oncogene，1996，13(8):1819-1830.
[110]Akashi H，Han HJ，Iizaka M，et al.Growth-suppressive effect of non-steroidal anti-inflammatory drugs on 11 colon-cancer cell lines and fluorescence differential display of genes whose expression is influenced by sulindac.International journal of cancer Journal international du cancer，2000，88(6):873-880.
[111]Coleman ML，Marshall CJ，Olson MF.RAS and RHO GTPases in G1-phase cell-cycle regulation.Nature reviews Molecular cell biology，2004，5(5):355-366.
[112]Decourt B，Bouleau Y，Dulon D，et al.Expression analysis of neuroleukin，calmodulin，cortactin，and Rho7/Rnd2 in the intact and injured mouse brain.Brain research Developmental brain research，2005，159(1):36-54.
[113]Huang H，Okamoto Y，Yokoo H，et al.Gene expression profiling and subgroup identification of oligodendrogliomas.Oncogene，2004，23(35):6012-6022.
[114]Pomeroy SL，Tamayo P，Gaasenbeek M，et al.Prediction of central nervous system embryonal tumour outcome based on gene expression.Nature，2002，415(6870):436-442.