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Pesquisa : D12.644.360.024.437 [Categoria DeCS]
Referências encontradas : 128 [refinar]
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[PMID]:28611052
[Au] Autor:Kim SB; Kim HR; Park MC; Cho S; Goughnour PC; Han D; Yoon I; Kim Y; Kang T; Song E; Kim P; Choi H; Mun JY; Song C; Lee S; Jung HS; Kim S
[Ad] Endereço:Medicinal Bioconvergence Research Center, Seoul National University, Suwon, South Korea.
[Ti] Título:Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells.
[So] Source:J Cell Biol;216(7):2201-2216, 2017 Jul 03.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRS-containing exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-α and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.
[Mh] Termos MeSH primário: Caspase 8/metabolismo
Neoplasias Colorretais/enzimologia
Exossomos/enzimologia
Mediadores da Inflamação/metabolismo
Lisina-tRNA Ligase/metabolismo
[Mh] Termos MeSH secundário: Animais
Caspase 8/genética
Quimiotaxia
Neoplasias Colorretais/genética
Neoplasias Colorretais/patologia
Neoplasias Colorretais/secreção
Exossomos/genética
Exossomos/patologia
Exossomos/secreção
Células HCT116
Seres Humanos
Lisina-tRNA Ligase/genética
Lisina-tRNA Ligase/secreção
Macrófagos/metabolismo
Camundongos
Complexos Multienzimáticos
Domínios PDZ
Ligação Proteica
Células RAW 264.7
Interferência de RNA
Transdução de Sinais
Sinteninas/metabolismo
Fatores de Tempo
Transfecção
Fator de Necrose Tumoral alfa/metabolismo
Fator de Necrose Tumoral alfa/secreção
[Pt] Tipo de publicação:JOURNAL ARTICLE; VIDEO-AUDIO MEDIA
[Nm] Nome de substância:
0 (Inflammation Mediators); 0 (Multienzyme Complexes); 0 (Syntenins); 0 (Tumor Necrosis Factor-alpha); EC 3.4.22.- (CASP8 protein, human); EC 3.4.22.- (Caspase 8); EC 6.1.1.6 (KRS protein, human); EC 6.1.1.6 (Lysine-tRNA Ligase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201605118


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[PMID]:28141839
[Au] Autor:Qian XL; Zhang J; Li PZ; Lang RG; Li WD; Sun H; Liu FF; Guo XJ; Gu F; Fu L
[Ad] Endereço:Department of Breast Pathology and Lab, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
[Ti] Título:Dasatinib inhibits c-src phosphorylation and prevents the proliferation of Triple-Negative Breast Cancer (TNBC) cells which overexpress Syndecan-Binding Protein (SDCBP).
[So] Source:PLoS One;12(1):e0171169, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Triple negative breast cancer (TNBC) progresses rapidly but lacks effective targeted therapies. Our previous study showed that downregulating syndecan-binding protein (SDCBP) in TNBC inhibits the proliferation of TNBC cells. Dasatinib is a new small-molecule inhibitor of c-src phosphorylation. The aim of this study was to investigate if SDCBP is a potential marker to indicate whether a TNBC is suitable for dasatinib therapy. This study applied co-immunoprecipitation to identify the interaction between SDCBP and c-src in TNBC cell lines. In addition, immunohistochemistry was used to investigate SDCBP and tyrosine-419 phosphorylated c-src (p-c-src-Y419) expression in TNBC tissues. SDCBP-overexpressing MDA-MB-231 cells were then constructed to evaluate the effects of dasatinib on SDCBP-induced TNBC progression in vitro and tumor formation in nude mice. We found wild-type SDCBP interacted with c-src and promoted the phosphorylation of c-src; this phosphorylation was completely blocked by dasatinib. SDCBP lacking the PDZ domain had no such effect. Among the 52 consecutive random TNBC cases examined, the expression of SDCBP was consistent with that of p-c-src-Y419, and positively correlated with histological grading or Ki-67 levels. SDCBP overexpression significantly accelerated the proliferation and cell cycle progression of the TNBC cell line MDA-MB-231; these effects were prevented by dasatinib treatment. However, the subsequent inhibition of p27 expression partially restored the proliferation and viability of the TNBC cells. The results of this study suggest that SDCBP interacts with c-src, regulates G1/S in TNBC cells, and enhances tumor cell proliferation by promoting the tyrosine phosphorylation of c-src at residue 419. Dasatinib inhibits such phosphorylation and blocks SDCBP-induced cell cycle progression. Therefore, SDCBP might be an important marker for identifying TNBC cases that are suitable for dasatinib therapy.
[Mh] Termos MeSH primário: Dasatinibe/farmacologia
Neoplasias de Mama Triplo Negativas/metabolismo
Neoplasias de Mama Triplo Negativas/patologia
Quinases da Família src/metabolismo
[Mh] Termos MeSH secundário: Animais
Carcinogênese/efeitos dos fármacos
Carcinogênese/metabolismo
Carcinogênese/patologia
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Dasatinibe/administração & dosagem
Progressão da Doença
Feminino
Seres Humanos
Camundongos Nus
Domínios PDZ
Fosforilação/efeitos dos fármacos
Ligação Proteica/efeitos dos fármacos
Sinteninas/química
Sinteninas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (SDCBP protein, human); 0 (Syntenins); EC 2.7.10.2 (CSK tyrosine-protein kinase); EC 2.7.10.2 (src-Family Kinases); RBZ1571X5H (Dasatinib)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171169


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[PMID]:27720715
[Au] Autor:Jana S; Sengupta S; Biswas S; Chatterjee A; Roy H; Bhattacharyya A
[Ad] Endereço:Immunology Laboratory, Department of Zoology, University of Calcutta, 35. B.C.Road, Kolkata, 700019, India.
[Ti] Título:miR-216b suppresses breast cancer growth and metastasis by targeting SDCBP.
[So] Source:Biochem Biophys Res Commun;482(1):126-133, 2017 Jan 01.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Breast cancer is the most deadly cancer among women and the second leading cause of cancer death worldwide. Treatment effectiveness is complicated with tumor invasiveness/drug resistance. To tailor treatments more effectively to individual patients, it is important to define tumor growth and metastasis at molecular levels. SDCBP is highly overexpressed and associated with a strikingly poor prognosis in breast cancer. However the post transcriptional regulation of SDCBP overexpression remains to be an unexplored area. Our study reveals that miR-216b directly regulates SDCBP expression by binding to its 3'UTR region. miR-216b is a tumor suppressive miRNA and it is underexpressed during metastatic breast cancer. Consequently, overexpression of miR-216b resulted in decreased proliferation, migration and invasion in BC cell lines by modulating the expression of SDCBP. Inhibition of miR-216b divergent the tumor suppressive role by inducing the growth proliferation, migration and invasion in vitro. There is therefore a negative correlation between the expression of miR-216b and its target gene SDCBP in the BC tissue samples as well as cell lines. Simultaneous expression of miR-216b and SDCBP rescued the growth, migration and invasion effect suggesting that tumor suppressive action of miR-216b may be directly mediated by SDCBP. In summary, the study identifies miR-216b as a regulator of SDCBP expression in breast cancer which can potentially be targeted for developing newer therapies for the effective treatment of this killer disease.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Neoplasias da Mama/secundário
Proliferação Celular/genética
Genes Supressores de Tumor
MicroRNAs/metabolismo
Sinteninas/genética
[Mh] Termos MeSH secundário: Neoplasias da Mama/patologia
Feminino
Seres Humanos
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN216 microRNA, human); 0 (MicroRNAs); 0 (SDCBP protein, human); 0 (Syntenins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170529
[Lr] Data última revisão:
170529
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161011
[St] Status:MEDLINE


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[PMID]:27589080
[Au] Autor:Fares J; Kashyap R; Zimmermann P
[Ad] Endereço:a Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068-CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes , Marseille , France.
[Ti] Título:Syntenin: Key player in cancer exosome biogenesis and uptake?
[So] Source:Cell Adh Migr;11(2):124-126, 2017 Mar 04.
[Is] ISSN:1933-6926
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer exosomes are gaining considerable amount of attention in basic and applied clinical research for their established role in the modulation of the tumor niche, and their broad-range contribution to tumor-host cross-talk. Supporting evidence to their role in tumorigenesis comes from the observation that exosome secretion, composition and functional effects are all altered as tumors become more aggressive. At the molecular level, the mechanisms underlying exosome biogenesis and uptake are far from being understood. Recent work has highlighted the critical role for the small intracellular adaptor protein syntenin in the biogenesis of a subset of exosomes and loading of cargo. Here, we review this recent work and some unpublished data that further highlight the possible implications of syntenin and the syndecan (SDC) heparan sulphate proteoglycans during exosome uptake, suggesting a supporting role for this pathway in the entire life cycle of cancer exosomes.
[Mh] Termos MeSH primário: Exossomos/metabolismo
Neoplasias/metabolismo
Sinteninas/metabolismo
[Mh] Termos MeSH secundário: Animais
Endossomos/metabolismo
Homeostase
Seres Humanos
Lisossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Syntenins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160903
[St] Status:MEDLINE
[do] DOI:10.1080/19336918.2016.1225632


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[PMID]:27802291
[Au] Autor:Walter RF; Werner R; Vollbrecht C; Hager T; Flom E; Christoph DC; Schmeller J; Schmid KW; Wohlschlaeger J; Mairinger FD
[Ad] Endereço:Ruhrlandklinik, West German Lung Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
[Ti] Título:ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP Were Identified as Reference Genes in Neuroendocrine Lung Cancer via the nCounter Technology.
[So] Source:PLoS One;11(11):e0165181, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Neuroendocrine lung cancer (NELC) represents 25% of all lung cancer cases and large patient collectives exist as formalin-fixed, paraffin-embedded (FFPE) tissue only. FFPE is controversially discussed as source for molecular biological analyses and reference genes for NELC are poorly establishes. MATERIAL AND METHODS: Forty-three representative FFPE-specimens were used for mRNA expression analysis using the digital nCounter technology (NanoString). Based on recent literature, a total of 91 mRNA targets were investigated as potential tumor markers or reference genes. The geNorm, NormFinder algorithms and coefficient of correlation were used to identify the most stable reference genes. Statistical analysis was performed by using the R programming environment (version 3.1.1). RESULTS: RNA integrity (RIN) ranged from 1.8 to 2.6 and concentrations from 34 to 2,109 ng/µl. However, the nCounter technology gave evaluable results for all samples tested. ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP were identified as constantly expressed genes with high stability (M-)values according to geNorm, NormFinder and coefficients of correlation. CONCLUSION: FFPE-derived mRNA is suitable for molecular biological investigations via the nCounter technology, although it is highly degraded. ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP are potent reference genes in neuroendocrine tumors of the lung.
[Mh] Termos MeSH primário: Inibidor de Quinase Dependente de Ciclina p27/genética
Proteína Adaptadora GRB2/genética
Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética
Neoplasias Pulmonares/genética
Tumores Neuroendócrinos/genética
Sinteninas/genética
Proteína rhoA de Ligação ao GTP/genética
[Mh] Termos MeSH secundário: Expressão Gênica/genética
Regulação Neoplásica da Expressão Gênica/genética
Seres Humanos
Inclusão em Parafina/métodos
RNA Mensageiro/genética
Fixação de Tecidos/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDKN1B protein, human); 0 (GRB2 Adaptor Protein); 0 (GRB2 protein, human); 0 (RNA, Messenger); 0 (SDCBP protein, human); 0 (Syntenins); 124671-05-2 (RHOA protein, human); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); EC 1.2.1.12 (Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)); EC 3.6.5.2 (rhoA GTP-Binding Protein)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161102
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0165181


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[PMID]:27358447
[Au] Autor:Munch AS; Kedar GH; van Weering JR; Vazquez-Sanchez S; He E; André T; Braun T; Söllner TH; Verhage M; Sørensen JB
[Ad] Endereço:Neurosecretion Group, Department of Neuroscience and Pharmacology, University of Copenhagen, DK-2200 Copenhagen N, Denmark, Center for Biomembranes in Nanomedicine, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
[Ti] Título:Extension of Helix 12 in Munc18-1 Induces Vesicle Priming.
[So] Source:J Neurosci;36(26):6881-91, 2016 Jun 29.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Munc18-1 is essential for vesicle fusion and participates in the docking of large dense-core vesicles to the plasma membrane. Recent structural data suggest that conformational changes in the 12th helix of the Munc18-1 domain 3a within the Munc18-1:syntaxin complex result in an additional interaction with synaptobrevin-2/VAMP2 (vesicle-associated membrane protein 2), leading to SNARE complex formation. To test this hypothesis in living cells, we examined secretion from Munc18-1-null mouse adrenal chromaffin cells expressing Munc18-1 mutants designed to either perturb the extension of helix 12 (Δ324-339), block its interaction with synaptobrevin-2 (L348R), or extend the helix to promote coil-coil interactions with other proteins (P335A). The mutants rescued vesicle docking and syntaxin-1 targeting to the plasma membrane, with the exception of P335A that only supported partial syntaxin-1 targeting. Disruptive mutations (L348R or Δ324-339) lowered the secretory amplitude by decreasing vesicle priming, whereas P335A markedly increased priming and secretory amplitude. The mutants displayed unchanged kinetics and Ca(2+) dependence of fusion, indicating that the mutations specifically affect the vesicle priming step. Mutation of a nearby tyrosine (Y337A), which interacts with closed syntaxin-1, mildly increased secretory amplitude. This correlated with results from an in vitro fusion assay probing the functions of Munc18-1, indicating an easier transition to the extended state in the mutant. Our findings support the notion that a conformational transition within the Munc18-1 domain 3a helix 12 leads to opening of a closed Munc18-1:syntaxin complex, followed by productive SNARE complex assembly and vesicle priming. SIGNIFICANCE STATEMENT: The essential postdocking role of Munc18-1 in vesicular exocytosis has remained elusive, but recent data led to the hypothesis that the extension of helix 12 in Munc18 within domain 3a leads to synaptobrevin-2/VAMP2 interaction and SNARE complex formation. Using both lack-of-function and gain-of-function mutants, we here report that the conformation of helix 12 predicts vesicle priming and secretory amplitude in living chromaffin cells. The effects of mutants on secretion could not be explained by differences in syntaxin-1 chaperoning/localization or vesicle docking, and the fusion kinetics and calcium dependence were unchanged, indicating that the effect of helix 12 extension is specific for the vesicle-priming step. We conclude that a conformational change within helix 12 is responsible for the essential postdocking role of Munc18-1 in neurosecretion.
[Mh] Termos MeSH primário: Proteínas Munc18/metabolismo
Estrutura Terciária de Proteína/fisiologia
Vesículas Secretórias/metabolismo
Sinteninas/metabolismo
[Mh] Termos MeSH secundário: Animais
Membrana Celular/ultraestrutura
Células Cultivadas
Células Cromafins/metabolismo
Células Cromafins/ultraestrutura
Embrião de Mamíferos
Feminino
Masculino
Camundongos
Camundongos Transgênicos
Modelos Moleculares
Proteínas Munc18/genética
Mutação/genética
Técnicas de Patch-Clamp
Estrutura Terciária de Proteína/genética
Proteínas Qa-SNARE/genética
Proteínas Qa-SNARE/metabolismo
Proteínas SNARE/metabolismo
Vesículas Secretórias/genética
Vesículas Secretórias/ultraestrutura
Sinteninas/genética
Transfecção
Proteína 2 Associada à Membrana da Vesícula/genética
Proteína 2 Associada à Membrana da Vesícula/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Munc18 Proteins); 0 (Qa-SNARE Proteins); 0 (SNARE Proteins); 0 (Stxbp1 protein, mouse); 0 (Syntenins); 0 (Vesicle-Associated Membrane Protein 2)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160701
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.0007-16.2016


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[PMID]:26787460
[Au] Autor:Garrido-Urbani S; Garg P; Ghossoub R; Arnold R; Lembo F; Sundell GN; Kim PM; Lopez M; Zimmermann P; Sidhu SS; Ivarsson Y
[Ad] Endereço:Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Aix-Marseille University, Centre National de la Recherche Scientifique UMR7258, Marseille, France.
[Ti] Título:Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin.
[So] Source:FEBS Lett;590(1):3-12, 2016 Jan.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Syntenin has crucial roles in cell adhesion, cell migration and synaptic transmission. Its closely linked postsynaptic density-95, discs large 1, zonula occludens-1 (PDZ) domains typically interact with C-terminal ligands. We profile syntenin PDZ1-2 through proteomic peptide phage display (ProP-PD) using a library that displays C-terminal regions of the human proteome. The protein recognizes a broad range of peptides, with a preference for hydrophobic motifs and has a tendency to recognize cryptic internal ligands. We validate the interaction with nectin-1 through orthogonal assays. The study demonstrates the power of ProP-PD as a complementary approach to uncover interactions of potential biological relevance.
[Mh] Termos MeSH primário: Modelos Moleculares
Sinteninas/metabolismo
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Animais
Sítios de Ligação
Células COS
Moléculas de Adesão Celular/química
Moléculas de Adesão Celular/genética
Moléculas de Adesão Celular/metabolismo
Cercopithecus aethiops
Biologia Computacional
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Proteínas Imobilizadas/química
Proteínas Imobilizadas/genética
Proteínas Imobilizadas/metabolismo
Cinética
Ligantes
Células MCF-7
Nectinas
Domínios PDZ
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/classificação
Fragmentos de Peptídeos/metabolismo
Biblioteca de Peptídeos
Proteômica/métodos
Proteínas Recombinantes/química
Proteínas Recombinantes/classificação
Proteínas Recombinantes/metabolismo
Sinteninas/química
Sinteninas/genética
Técnicas do Sistema de Duplo-Híbrido
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Cell Adhesion Molecules); 0 (Immobilized Proteins); 0 (Ligands); 0 (NECTIN1 protein, human); 0 (Nectins); 0 (Peptide Fragments); 0 (Peptide Library); 0 (Recombinant Proteins); 0 (SDCBP protein, human); 0 (Syntenins)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160121
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12037


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[PMID]:26561205
[Au] Autor:Wang LK; Pan SH; Chang YL; Hung PF; Kao SH; Wang WL; Lin CW; Yang SC; Liang CH; Wu CT; Hsiao TH; Hong TM; Yang PC
[Ad] Endereço:Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
[Ti] Título:MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma.
[So] Source:Oncotarget;7(1):386-401, 2016 Jan 05.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal-transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis.
[Mh] Termos MeSH primário: Adenocarcinoma/genética
Transição Epitelial-Mesenquimal/genética
Neoplasias Pulmonares/genética
Sinteninas/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Adenocarcinoma/metabolismo
Adenocarcinoma/patologia
Animais
Linhagem Celular Tumoral
Feminino
Regulação Neoplásica da Expressão Gênica
Células HEK293
Seres Humanos
Immunoblotting
Neoplasias Pulmonares/metabolismo
Neoplasias Pulmonares/patologia
Células MCF-7
Masculino
Camundongos Endogâmicos NOD
Camundongos SCID
Microscopia Confocal
Invasividade Neoplásica
Metástase Neoplásica
Ligação Proteica
Interferência de RNA
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Fatores de Transcrição da Família Snail
Análise de Sobrevida
Sinteninas/metabolismo
Fatores de Transcrição/metabolismo
Transplante Heterólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (SDCBP protein, human); 0 (SNAI1 protein, human); 0 (Snai2 protein, mouse); 0 (Snail Family Transcription Factors); 0 (Syntenins); 0 (Transcription Factors)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:170103
[Lr] Data última revisão:
170103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151113
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.6299


  9 / 128 MEDLINE  
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[PMID]:26291527
[Au] Autor:Philley JV; Kannan A; Dasgupta S
[Ad] Endereço:Department of Medicine, The University of Texas Health Science Center at Tyler, Tyler, Texas.
[Ti] Título:MDA-9/Syntenin Control.
[So] Source:J Cell Physiol;231(3):545-50, 2016 Mar.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:MDA-9/Syntenin is a small PDZ domain containing scaffolding protein with diverse array of functions regulating membrane trafficking, cell adhesion, neural, and synaptic development, ubiquitination, and exosome biogenesis. An appreciable number of studies also established a pivotal role of MDA-9/Syntenin in cancer development and progression. In this review, we will discuss the dynamic role of MDA-9/Syntenin in regulating normal and abnormal fate of various cellular processes.
[Mh] Termos MeSH primário: Adesão Celular/fisiologia
Movimento Celular/fisiologia
Neoplasias/metabolismo
Sinteninas/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Ligação Proteica/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (SDCBP protein, human); 0 (Syntenins)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:151124
[Lr] Data última revisão:
151124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150821
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25136


  10 / 128 MEDLINE  
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[PMID]:25893292
[Au] Autor:Hwangbo C; Tae N; Lee S; Kim O; Park OK; Kim J; Kwon SH; Lee JH
[Ad] Endereço:Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do, Republic of Korea.
[Ti] Título:Syntenin regulates TGF-ß1-induced Smad activation and the epithelial-to-mesenchymal transition by inhibiting caveolin-mediated TGF-ß type I receptor internalization.
[So] Source:Oncogene;35(3):389-401, 2016 Jan 21.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Syntenin, a tandem PDZ domain containing scaffold protein, functions as a positive regulator of cancer cell progression in several human cancers. We report here that syntenin positively regulates transforming growth factor (TGF)-ß1-mediated Smad activation and the epithelial-to-mesenchymal transition (EMT) by preventing caveolin-1-mediated internalization of TGF-ß type I receptor (TßRI). Knockdown of syntenin suppressed TGF-ß1-mediated cell migration, transcriptional responses and Smad2/3 activation in various types of cells; however, overexpression of syntenin facilitated TGF-ß1-mediated responses. In particular, syntenin knockdown abolished both the basal and TGF-ß1-mediated repression of E-cadherin expression, as well as induction of vimentin expression along with Snail and Slug upregulation; thus, blocking the TGF-ß1-induced EMT in A549 cells. In contrast, overexpression of syntenin exhibited the opposite effect. Knockdown of syntenin-induced ubiquitination and degradation of TßRI, but not TGF-ß type II receptor, leading to decreased TßRI expression at the plasma membrane. Syntenin associated with TßRI at its C-terminal domain and a syntenin mutant lacking C-terminal domain failed to increase TGF-ß1-induced responses. Biochemical analyzes revealed that syntenin inhibited the interaction between caveolin-1 and TßRI and knockdown of syntenin induced a massive internalization of TßRI and caveolin-1 from lipid rafts, indicating that syntenin may increase TGF-ß signaling by inhibiting caveolin-1-dependent internalization of TßRI. Moreover, a positive correlation between syntenin expression and phospho-Smad2 levels is observed in human lung tumors. Taken together, these findings demonstrate that syntenin may act as an important positive regulator of TGF-ß signaling by regulating caveolin-1-mediated internalization of TßRI; thus, providing a novel function for syntenin that is linked to cancer progression.
[Mh] Termos MeSH primário: Caveolina 1/genética
Neoplasias Pulmonares/genética
Proteínas Serina-Treonina Quinases/genética
Receptores de Fatores de Crescimento Transformadores beta/genética
Sinteninas/genética
Fator de Crescimento Transformador beta1/genética
[Mh] Termos MeSH secundário: Caveolina 1/metabolismo
Linhagem Celular Tumoral
Movimento Celular/genética
Transição Epitelial-Mesenquimal/genética
Regulação Neoplásica da Expressão Gênica
Técnicas de Silenciamento de Genes
Seres Humanos
Neoplasias Pulmonares/patologia
Fosforilação
Proteínas Serina-Treonina Quinases/biossíntese
Receptores de Fatores de Crescimento Transformadores beta/biossíntese
Transdução de Sinais
Proteína Smad2/genética
Sinteninas/metabolismo
Fator de Crescimento Transformador beta1/metabolismo
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Caveolin 1); 0 (Receptors, Transforming Growth Factor beta); 0 (SMAD2 protein, human); 0 (Smad2 Protein); 0 (Syntenins); 0 (Transforming Growth Factor beta1); EC 2.7.1.11 (TGF-beta type I receptor); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.30 (transforming growth factor-beta type II receptor)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150421
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2015.100



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