{"database":"Cell Collective","file_versions":[],"scores":{"citationCount":22193,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"omics_type":["Models"],"submitter":["Audrey Crowther"],"version_name":[""],"full_dataset_link":["https://cellcollective.org/#7916/aurora-kinase-a-in-neuroblastoma"],"model_score":["24.960500000000003"],"default_version":["1"],"ModelFormat":["SBML"],"submitter_affiliation":[""],"submitter_email":[""],"version_id":["1"],"repository":["Cell Collective"],"version_url":["https://cellcollective.org/#7916:1/aurora-kinase-a-in-neuroblastoma"],"version_description":[""],"pubmed_abstract":["Aurora Kinase A (AURKA) is often overexpressed in neuroblastoma (NB) with poor outcome. The causes of AURKA overexpression in NB are unknown. Here, we describe a gene regulatory network consisting of core regulators of AURKA protein expression and activation during mitosis to identify potential causes. This network was transformed to a dynamic Boolean model. Simulated activation of the serine/threonine protein kinase Greatwall (GWL, encoded by MASTL) that attenuates the pivotal AURKA inhibitor PP2A, predicted stabilization of AURKA. Consistent with this notion, gene set enrichment analysis showed enrichment of mitotic spindle assembly genes and MYCN target genes in NB with high GWL/MASTL expression. In line with the prediction of GWL/MASTL enhancing AURKA, elevated expression of GWL/MASTL was associated with NB risk factors and poor survival of patients. These results establish Boolean network modeling of oncogenic pathways in NB as a useful means for guided discovery in this enigmatic cancer."],"pubmed_title":["Boolean modeling identifies Greatwall/MASTL as an important regulator in the AURKA network of neuroblastoma."],"pubmed_authors":["Dahlhaus Meike M, Burkovski Andre A, Hertwig Falk F, Mussel Christoph C, Volland Ruth R, Fischer Matthias M, Debatin Klaus-Michael KM, Kestler Hans A HA, Beltinger Christian C"],"description_synonyms":["PP2A[[C]], PR53, PR55, Materials, l(3)S026326, vif, PP2A[B], Phases, pr53, anon-WO0118547.420, Risk Factor Score, Tumor, 2-Amino-3-hydroxypropionic acid, 5730420M11Rik, DmelCG7109, B', Risk Factors, EP0515, l(3)S031807, PP2A 28D, PP2A[C], aurka-a, Kinase, l(3)01436, Threonin, l(3)S110815, Correlates, A, SET, AIRK1, M Phases, Pp2A, PP2a, l(3)S026226, l(3)S027313, Q, l(3)S141309, aar, MAST-L, Nmyc1, elevated, pp2a, l(3)02414, DmelCG4299, Social, DmelCG6235, set, PR65, l(3)S035505b, PP2A, Health Correlates, l(3)S048006, Pp2A-28D, l(3)S048013, Iak1, IAK1, PP2A[A], Tumors, l(3)S067915, Serine-Threonine Protein Kinase 15, CG7901, l(3)S091905, PP2-AB, predicted, aur-a, Aurora Kinases A, serine/threonine protein phosphatase 2A, Benign, Pk91C, 1466/06, DmPp2A-28D, l(3)S029403, l(3)S033903, activation, CG7913, xN-myc1, vif Genes, Q Genes, Wrd, HLA-DR-associated protein II, Social Risk Factors, Mitoses, death rate, DI-2, I-2Dm, RP11-85G18.2, l(3)S042630, pp2A-B', Benign Neoplasms, INSDC_feature:gene, I-2PP1, dPP2A A, l(3)S075902b, TAF-IBETA, wrd, STK15 Kinase, antagonists and inhibitors, A/PR65, SNF1-related protein kinase 2.2, Material, l(3)S066813, l(3)S027127, spindle organization and biogenesis in nucleus during mitosis, C88295, GW, B56-2, Mitotic, TAF-Ibeta, l(3)S042629, AURORA2, B56-1, l(3)S063110, LD02456, Nmyc, dPP2A-B56-1, dPP2A-B56-2, Neoplasms, ODED, CG5643, greatwall, STK15, sor Gene, protein-containing complex, l(3)S132907, AIK, 2700091H24Rik, Ark1, ARK1, l(3)S069206a, l(3)S023141a, NMYC, Gene Products, CG17291, ark1, i234, nmyc, CG7719, Risk Factor, l(3)S119908, aik, l(3)j11C8, BTAK Protein, l(3)S046918, PP2A[B'-1], l(3)S088513, dPP2A-Balpha, AURORA2 Protein, aura, 2pp2a, dPP2A-C, Nmuc1, 5559, GWL, BEST:LD02456, CG10574, Population at Risk, Neoplasias, PP2A[B'-2], DPR65, 2PP2A, l(3)S029110, dSET, dSet, bHLHe37, PP2Ac, ppp2r2c, high elevation, XNmyc, AURA, l(3)S076415, Cancer, inhibitors, l(3)S023938, DPR55, CG 7913, DmelCG7719, Malignant Neoplasm, aurora2, EP3559, Proteins, thc2, sor, Factor, Serin, SRK2D, DmelCG5643, MT, native protein, I-2PP2A, Dm I-2, chemical analysis, PP2A C, Neoplasm, PP2A A, Mitotic M Phase, NB, Q Gene, Phase, Serine Threonine Protein Kinase 15, l(2)02496, primary cancer, DmelCG17291, ensemble, l(2)s5286, l(3)S032303, l(3)S075110, Cancers, malignant tumor, tws/aar, mitotic spindle organization and biogenesis in nucleus, l(3)S105605, Gene Proteins, THC2, ppp2r2b-a, PROTEIN KINASE, Pp2A29B, Neoplasia, IPP2A2, l(3)S025913, determination, DmelCG7913, mycna, mycnb, L-Threonine, A Genes, protein, l(3)S060804, PPP1R47, l(3)S024838, l(3)S025806, Mitotic M, l(3)S045519, l(3)S043008b, Tws, IAK, 0318/07, PP2, l(3)S031006, l(3)S053011, l(3)S080409, protein aggregate, 1J, Aurora-A Kinase, spindle assembly involved in mitosis, CG7719-related, l(3)s1801, l(3)S049902, TAF-I, sor Genes, l(3)S067109b, mitotic spindle assembly, TYPE 2A SERINE/THREONINE PROTEIN PHOSPHATASE, MTS/PP2A, N-myc, IGAAD, 2-amino-3-hydroxypropanoic acid, v158, DmelCG10574, malignant neoplasm, XN-myc, R75353, Breast Tumor Amplified Kinase, F20P5.30, Malignancies, ER2-6, l(3)S043029, F20P5_30, phapii, l(3)S024834a, tw, PP2a 28D, l(3)S025832, l(3)S022440, CG7109, StF-IT-1, B/PR55, l(3)S101413b, Pp2A-85F, results, l(3)S023309, anon-WO2004063362.73, l(3)S110008a, 3-Hydroxyalanine, Genetic Materials, Score, BcDNA:LD34343, Genetic Material, l(3)S029701a, ptpa, PP2A B', mitotic spindle organisation in nucleus, Breast-Tumor-Amplified Kinase, Factors, Risk, Neuroblastomas, PTPA, CG6235, l(3)S061915, CG4299, CG33297, l(3)S066017, l(3)S032708c, mitotic spindle organization and biogenesis in cell nucleus, Social Risk, ARK-1, SNF1-RELATED PROTEIN KINASE 2-2, l(3)S023206, Health, Patient, l(3)S134601a, l(3)S022361, L Serine, Cistron, l(3)S061805, L-Serine, Protein Kinase, i2pp2a, Malignant Neoplasms., AuroraA Kinase, Microtubule-associated serine|threonine-protein kinase-like, Aurora-A, Pk?2, vif Gene, PP2A-29B, Benign Neoplasm, Gene, scant, Wdb, dPP2A, l(3)S075515b, l(3)S111515, Malignant, CG13383, PHAPII, AU019385, dPR55, mycn, l(3)S048507, AW539821, dB56-2, dB56-1, BcDNA:GM05554, PP2A-A, B'/PR61, stk15, PP2A-B, l(3)S022205b, PP2A-C, Populations at Risk, Genetic, STK6, l(3)S146606, Malignancy, Stk6, STK7, ipp2a2, inhibiteur, Risk Score, L Threonine, ATP-protein phosphotransferase, Ayk1, MODED, SNRK2-2, inhibidor, taf-ibeta, GREATWALL, time of survival, Clients, l(3)S024455, Social Risk Factor, stk6, stk7, A Gene, l(3)S060203, protein complex, Mts, l(3)S023013, igaad, inhibitor, CT23435, l(3)S028707, Cistrons, Risk Factor Scores, l(3)S052810, Client, group, 2.7.11.1, Aurora A Kinases, survival, mitosis, Protein, c-nmyc, I2PP2A, Eg2, core, Aurora A Kinase, M Phase, antagonists, hGWL, Genes, SPK-2-2, Neuroblastoma, Kinases, AURKA, btak, Nmyc-1, Risk Scores, Protein Gene Products, BTAK, dSET/TAF-Ibeta, 2610030F17Rik, Mitotic M Phases, 2414, 6330556D22Rik, assay, AA407739"],"pubmed_title_synonyms":["AuroraA Kinase, Serine-Threonine Protein Kinase 15, Aurora-A, aurora2, Neuroblastoma., greatwall, thc2, STK15, AU019385, aur-a, PPP1R47, AIK, Aurora Kinases A, 2700091H24Rik, Aurora A Kinases, Ark1, ARK1, Eg2, IAK, Aurora A Kinase, aurka-a, NB, AW539821, regulator, ark1, Aurora-A Kinase, aik, BTAK Protein, hGWL, Serine Threonine Protein Kinase 15, stk15, AIRK1, Breast-Tumor-Amplified Kinase, STK6, Neuroblastomas, Stk6, STK7, AURORA2 Protein, aura, RP11-85G18.2, AURKA, btak, MAST-L, GWL, Ayk1, BTAK, THC2, ARK-1, STK15 Kinase, GREATWALL, C88295, GW, Breast Tumor Amplified Kinase, stk6, AURORA2, stk7, Iak1, IAK1, AURA"],"name_synonyms":["BTAK Protein, Serine Threonine Protein Kinase 15, AIRK1, AuroraA Kinase, Breast-Tumor-Amplified Kinase, Serine-Threonine Protein Kinase 15, STK6, Neuroblastomas, AURORA2 Protein, AURKA, Neuroblastoma., STK15, Ayk1, BTAK, AIK, Aurora Kinases A, Aurora A Kinases, ARK1, STK15 Kinase, Breast Tumor Amplified Kinase, Aurora A Kinase, NB, Iak1, AURA, Aurora-A Kinase"],"pubmed_abstract_synonyms":["PP2A[[C]], PR53, Materials, PR55, l(3)S026326, PP2A[B], Phases, pr53, anon-WO0118547.420, Risk Factor Score, Tumor, 2-Amino-3-hydroxypropionic acid, 5730420M11Rik, DmelCG7109, B', Risk Factors, EP0515, l(3)S031807, PP2A 28D, PP2A[C], aurka-a, Kinase, l(3)01436, Threonin, l(3)S110815, Correlates, SET, AIRK1, M Phases, Pp2A, PP2a, l(3)S026226, l(3)S027313, l(3)S141309, aar, MAST-L, Nmyc1, elevated, pp2a, l(3)02414, DmelCG4299, Social, DmelCG6235, set, PR65, l(3)S035505b, PP2A, Health Correlates, l(3)S048006, Pp2A-28D, l(3)S048013, Iak1, IAK1, PP2A[A], Tumors, l(3)S067915, Serine-Threonine Protein Kinase 15, CG7901, l(3)S091905, PP2-AB, predicted, aur-a, Aurora Kinases A, serine/threonine protein phosphatase 2A, Benign, Pk91C, 1466/06, DmPp2A-28D, l(3)S029403, l(3)S033903, activation, CG7913, xN-myc1, Wrd, HLA-DR-associated protein II, Social Risk Factors, Mitoses, death rate, DI-2, I-2Dm, RP11-85G18.2, l(3)S042630, pp2A-B', Benign Neoplasms, INSDC_feature:gene, I-2PP1, dPP2A A, l(3)S075902b, TAF-IBETA, wrd, STK15 Kinase, antagonists and inhibitors, A/PR65, Material, SNF1-related protein kinase 2.2, l(3)S066813, l(3)S027127, spindle organization and biogenesis in nucleus during mitosis, C88295, GW, B56-2, Mitotic, TAF-Ibeta, l(3)S042629, AURORA2, B56-1, l(3)S063110, LD02456, Nmyc, dPP2A-B56-1, dPP2A-B56-2, Neoplasms, ODED, CG5643, greatwall, STK15, protein-containing complex, l(3)S132907, AIK, 2700091H24Rik, Ark1, ARK1, l(3)S069206a, l(3)S023141a, NMYC, Gene Products, CG17291, ark1, i234, nmyc, CG7719, Risk Factor, l(3)S119908, aik, l(3)j11C8, BTAK Protein, l(3)S046918, PP2A[B'-1], l(3)S088513, dPP2A-Balpha, AURORA2 Protein, aura, 2pp2a, dPP2A-C, Nmuc1, 5559, GWL, BEST:LD02456, CG10574, Population at Risk, Neoplasias, PP2A[B'-2], DPR65, 2PP2A, l(3)S029110, dSET, dSet, bHLHe37, PP2Ac, ppp2r2c, high elevation, XNmyc, AURA, l(3)S076415, Cancer, inhibitors, l(3)S023938, DPR55, CG 7913, DmelCG7719, Malignant Neoplasm, aurora2, EP3559, Proteins, thc2, Factor, Serin, SRK2D, DmelCG5643, MT, native protein, I-2PP2A, Dm I-2, chemical analysis, PP2A C, Neoplasm, PP2A A, Mitotic M Phase, NB, Phase, Serine Threonine Protein Kinase 15, l(2)02496, primary cancer, DmelCG17291, ensemble, l(2)s5286, l(3)S032303, l(3)S075110, Cancers, malignant tumor, tws/aar, mitotic spindle organization and biogenesis in nucleus, l(3)S105605, Gene Proteins, THC2, ppp2r2b-a, PROTEIN KINASE, Pp2A29B, Neoplasia, IPP2A2, l(3)S025913, determination, DmelCG7913, mycna, mycnb, L-Threonine, protein, l(3)S060804, PPP1R47, l(3)S024838, l(3)S025806, Mitotic M, l(3)S045519, l(3)S043008b, pathogenesis, Tws, IAK, 0318/07, PP2, l(3)S031006, l(3)S053011, l(3)S080409, protein aggregate, 1J, Aurora-A Kinase, spindle assembly involved in mitosis, CG7719-related, l(3)s1801, l(3)S049902, TAF-I, l(3)S067109b, mitotic spindle assembly, TYPE 2A SERINE/THREONINE PROTEIN PHOSPHATASE, MTS/PP2A, N-myc, IGAAD, 2-amino-3-hydroxypropanoic acid, v158, DmelCG10574, malignant neoplasm, XN-myc, R75353, Breast Tumor Amplified Kinase, F20P5.30, Malignancies, ER2-6, l(3)S043029, F20P5_30, phapii, l(3)S024834a, tw, PP2a 28D, l(3)S025832, l(3)S022440, CG7109, StF-IT-1, B/PR55, l(3)S101413b, Pp2A-85F, results, l(3)S023309, anon-WO2004063362.73, l(3)S110008a, 3-Hydroxyalanine, Genetic Materials, Score, Genetic Material, BcDNA:LD34343, l(3)S029701a, ptpa, PP2A B', mitotic spindle organisation in nucleus, Breast-Tumor-Amplified Kinase, Factors, Risk, Neuroblastomas, PTPA, CG6235, l(3)S061915, CG4299, CG33297, l(3)S066017, l(3)S032708c, mitotic spindle organization and biogenesis in cell nucleus, Social Risk, ARK-1, SNF1-RELATED PROTEIN KINASE 2-2, l(3)S023206, Health, Patient, l(3)S134601a, l(3)S022361, Cistron, L Serine, l(3)S061805, L-Serine, Protein Kinase, i2pp2a, Malignant Neoplasms., AuroraA Kinase, Microtubule-associated serine|threonine-protein kinase-like, Aurora-A, Pk?2, PP2A-29B, Benign Neoplasm, Gene, scant, Wdb, dPP2A, l(3)S075515b, l(3)S111515, Malignant, CG13383, PHAPII, AU019385, dPR55, mycn, l(3)S048507, AW539821, dB56-2, dB56-1, BcDNA:GM05554, PP2A-A, B'/PR61, stk15, PP2A-B, l(3)S022205b, PP2A-C, Populations at Risk, Genetic, STK6, l(3)S146606, Malignancy, Stk6, STK7, ipp2a2, inhibiteur, Risk Score, causes, L Threonine, ATP-protein phosphotransferase, Ayk1, MODED, SNRK2-2, inhibidor, taf-ibeta, GREATWALL, time of survival, Clients, l(3)S024455, causality, Social Risk Factor, stk6, stk7, l(3)S060203, protein complex, Mts, l(3)S023013, igaad, inhibitor, CT23435, l(3)S028707, Cistrons, Risk Factor Scores, l(3)S052810, Client, group, 2.7.11.1, Aurora A Kinases, survival, mitosis, Protein, c-nmyc, I2PP2A, Eg2, core, Aurora A Kinase, M Phase, antagonists, hGWL, SPK-2-2, Neuroblastoma, Kinases, AURKA, btak, Nmyc-1, Risk Scores, Protein Gene Products, BTAK, dSET/TAF-Ibeta, 2610030F17Rik, Mitotic M Phases, 2414, 6330556D22Rik, assay, AA407739"],"citation_count":["22193"],"additional_accession":[]},"is_claimable":false,"name":"Aurora Kinase A in Neuroblastoma","description":"Aurora Kinase A (AURKA) is often overexpressed in neuroblastoma (NB) with poor outcome. The causes of AURKA overexpression in NB are unknown. Here, we describe a gene regulatory network consisting of core regulators of AURKA protein expression and activation during mitosis to identify potential causes. This network was transformed to a dynamic Boolean model. Simulated activation of the serine/threonine protein kinase Greatwall (GWL, encoded by MASTL) that attenuates the pivotal AURKA inhibitor PP2A, predicted stabilization of AURKA. Consistent with this notion, gene set enrichment analysis showed enrichment of mitotic spindle assembly genes and MYCN target genes in NB with high GWL/MASTL expression. In line with the prediction of GWL/MASTL enhancing AURKA, elevated expression of GWL/MASTL was associated with NB risk factors and poor survival of patients. These results establish Boolean network modeling of oncogenic pathways in NB as a useful means for guided discovery in this enigmatic cancer.","dates":{"created":"2017-04-20","publication":"","submission":"2018-04-23","last_modified":"2018-04-23"},"accession":"7916","cross_references":{"pubmed":["26616283"]}}