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[PMID]:29185092
[Au] Autor:Ma M; Dai J; Xu T; Yu S; Yu H; Tang H; Yan J; Wu X; Yu J; Chi Z; Si L; Cui C; Sheng X; Kong Y; Guo J
[Ad] Endereço:Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Beijing, 100142, China.
[Ti] Título:Analysis of TSC1 mutation spectrum in mucosal melanoma.
[So] Source:J Cancer Res Clin Oncol;144(2):257-267, 2018 Feb.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Mucosal melanoma is a relatively rare subtype of melanoma for which no clearly established therapeutic strategy exists. The genes of the mTOR signalling pathway have drawn great attention as key targets for cancer treatment, including melanoma. In this study, we aimed to investigate the mutation status of the upstream mTOR regulator TSC1 and evaluated its correlation with the clinicopathological features of mucosal melanoma. METHODS: We collected 91 mucosal melanoma samples for detecting TSC1 mutations. All the coding exons of TSC1 were amplified by PCR and subjected to Sanger sequencing. Expression level of TSC1 encoding protein (hamartin) was detected by immunohistochemistry. The activation of mTOR pathway was determined by evaluating the phosphorylation status of S6RP and 4E-BP1. RESULTS: The overall mutation frequency of TSC1 was found to be 17.6% (16/91 patients). TSC1 mutations were more inclined to occur in advanced mucosal melanoma (stages III and IV). In the 16 patients with TSC1 mutations, 14 different mutations were detected, affecting 11 different exons. TSC1 mutations were correlated with upregulation of S6RP phosphorylation but were unrelated to 4E-BP1 phosphorylation or hamartin expression. Mucosal melanoma patients with TSC1 mutations had a worse outcome than patients without TSC1 mutations (24.0 versus 34.0 months, P = 0.007). CONCLUSIONS: Our findings suggest that TSC1 mutations are frequent in mucosal melanoma. TSC1 mutations can activate the mTOR pathway through phospho-S6RP and might be a poor prognostic predictor of mucosal melanoma. Our data implicate the potential significance of TSC1 mutations for effective and specific drug therapy for mucosal melanoma.
[Mh] Termos MeSH primário: Melanoma/genética
Mutação
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Análise Mutacional de DNA
Feminino
Seres Humanos
Masculino
Melanoma/metabolismo
Melanoma/patologia
Meia-Idade
Membrana Mucosa/patologia
Estadiamento de Neoplasias
Fosfoproteínas/metabolismo
Prognóstico
Proteína S6 Ribossômica/metabolismo
Serina-Treonina Quinases TOR/metabolismo
Proteínas Supressoras de Tumor/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (EIF4EBP1 protein, human); 0 (Phosphoproteins); 0 (Ribosomal Protein S6); 0 (Tumor Suppressor Proteins); 0 (tuberous sclerosis complex 1 protein); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2550-z


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[PMID]:29028222
[Au] Autor:Choi HJ; Joo HS; Won HY; Min KW; Kim HY; Son T; Oh YH; Lee JY; Kong G
[Ad] Endereço:Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University,
[Ti] Título:Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.
[So] Source:J Natl Cancer Inst;110(4), 2018 Apr 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase assay were performed to identify the tamoxifen resistance mechanism by RBP2. All statistical tests were two-sided. Results: RBP2 was associated with poor prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore, RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity, whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9] mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P < .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors and regulated several tamoxifen resistance-associated genes, including NRIP1, CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R) activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT activation via demethylase activity-independent ErbB protein stabilization. Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2-mediated tamoxifen resistance (RBP2-overexpressing cells: % cell viability [SD], tamoxifen = 89.0 [3.8]%, vs tamoxifen with BKM120 = 41.3 [5.6]%, P < .001). Conclusions: RBP2 activates ER-IGF1R-ErbB signaling cascade in multiple ways to induce tamoxifen resistance, suggesting that RBP2 is a potential therapeutic target for ER-driven cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Carcinoma Ductal de Mama/metabolismo
Resistência a Medicamentos Antineoplásicos
Proteínas de Neoplasias/fisiologia
Receptores Estrogênicos/metabolismo
Proteína 2 de Ligação ao Retinoblastoma/fisiologia
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Análise de Variância
Animais
Antineoplásicos Hormonais/uso terapêutico
Neoplasias da Mama/química
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/patologia
Carcinoma Ductal de Mama/química
Carcinoma Ductal de Mama/tratamento farmacológico
Carcinoma Ductal de Mama/patologia
Proteínas de Transporte/metabolismo
Estudos de Coortes
Colorimetria
Intervalo Livre de Doença
Resistência a Medicamentos Antineoplásicos/genética
Feminino
Xenoenxertos
Seres Humanos
Estimativa de Kaplan-Meier
Células MCF-7
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Proteínas de Neoplasias/metabolismo
Células-Tronco Neoplásicas
Proteínas Nucleares/metabolismo
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/metabolismo
Receptor ErbB-2/metabolismo
Receptor IGF Tipo 1/metabolismo
Proteína 2 de Ligação ao Retinoblastoma/metabolismo
Tamoxifeno/uso terapêutico
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Antineoplastic Agents, Hormonal); 0 (Carrier Proteins); 0 (IGFBP5-interacting protein, human); 0 (Neoplasm Proteins); 0 (Nuclear Proteins); 0 (Receptors, Estrogen); 0 (nuclear receptor interacting protein 1); 094ZI81Y45 (Tamoxifen); EC 1.14.11.27 (Retinoblastoma-Binding Protein 2); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.1 (Receptor, ErbB-2); EC 2.7.10.1 (Receptor, IGF Type 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx207


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[PMID]:28747736
[Au] Autor:Li Y; Cheng H; Xiao FL; Liang B; Zhou FS; Li P; Zheng XD; Sun LD; Yang S; Zhang XJ
[Ad] Endereço:Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui, China.
[Ti] Título:Association of UBASH3A gene polymorphism and atopic dermatitis in the Chinese Han population.
[So] Source:Genes Immun;18(3):158-162, 2017 09.
[Is] ISSN:1476-5470
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Genome-wide association studies have revealed a large number of genetic-risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases share susceptibility loci. Recent evidence has demonstrated that UBASH3A gene was associated with multiple autoimmune diseases. The aim of this study was to explore the association between UBASH3A single-nucleotide polymorphisms (SNPs) and atopic dermatitis (AD) in a Chinese Han population. In total, three UBASH3A SNPs (rs11203203, rs3788013 and rs1893592) were genotyped using TaqMan genotyping assays in a Chinese Han population (1012 cases and 1362 controls). Among these SNPs, we selected the SNP rs1893592 with association values of P<5 × 10 for AD in the TaqMan genotyping assay data for further replication in the independent Chinese replication samples (1080 cases and 1367 controls) using a Sequenom MassARRAY system. We combined the association results in two stages using meta-analysis. We found that rs1893592 in UBASH3A showed association with AD (P=1.29 × 10 , odds ratio=1.16). These results showed that UBASH3A gene SNP is associated with susceptibility to AD. Further fine mapping and functional studies will be required to identify true causal variant in the UBASH3A gene and its exact role in the pathogenesis of AD.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/genética
Dermatite Atópica/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Adulto
Estudos de Casos e Controles
Criança
Pré-Escolar
China
Feminino
Seres Humanos
Lactente
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (UBASH3A protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1038/gene.2017.15


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[PMID]:28455144
[Au] Autor:Zhang F; Lu YX; Chen Q; Zou HM; Zhang JM; Hu YH; Li XM; Zhang WJ; Zhang W; Lin C; Li XN
[Ad] Endereço:Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: zfan1985@yeah.net.
[Ti] Título:Identification of NCK1 as a novel downstream effector of STAT3 in colorectal cancer metastasis and angiogenesis.
[So] Source:Cell Signal;36:67-78, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Signal transducer and activator of transcription 3 (STAT3) is known to activate targets associated with invasion, proliferation, and angiogenesis in a wide variety of cancers. The adaptor protein NCK1 is involved in cytoskeletal movement and was identified as a STAT3-associated target in human tumors. However, the underlying molecular mechanism associated with colorectal cancer (CRC) metastasis is not yet completely understood. In this study, we report a novel STAT3 to NCK1 signaling pathway in colorectal cancer (CRC). We investigated the expression of NCK1 and its potential clinical and biological significance in CRC. NCK1 was noticeably up-regulated in human CRC tissues. NCK1 was also significantly associated with serosal invasion, lymph metastasis, and tumor-node-metastasis classification but was inversely correlated with differentiation. Gain-of-function and loss-of-function studies have shown that ectopic expression of NCK1 enhanced metastasis and angiogenesis in CRC cells. By gene expression analyses, we revealed a high co-overexpression of STAT3 and NCK1 in CRC tissues. Ectopic overexpression of STAT3 in CRC cells induced the expression of NCK1, whereas STAT3 knockdown decreased the expression of NCK1. Promoter activation and binding analyses demonstrated that STAT3 promoted the expression of NCK1 via direct action on the NCK1 promoter. The knock down of NCK1 partially reduced the CRC cell metastasis and angiogenesis promoted by STAT3. Additionally, by co-immunoprecipitation assays, we verified that NCK1 interacted with PAK1, which resulted in the activation of the PAK1/ERK pathway. STAT3 induced the transcription of NCK1 and triggered a PAK1/ERK cascade in CRC. These findings suggest a novel STAT3 to NCK1 to PAK1/ERK signaling mechanism that is potentially critical for CRC metastasis and angiogenesis.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Neoplasias Colorretais/irrigação sanguínea
Neoplasias Colorretais/patologia
Metástase Linfática/patologia
Neovascularização Patológica/metabolismo
Proteínas Oncogênicas/metabolismo
Fator de Transcrição STAT3/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Animais
Movimento Celular
Galinhas
Neoplasias Colorretais/genética
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Feminino
Quinase 2 de Adesão Focal/metabolismo
Regulação Neoplásica da Expressão Gênica
Técnicas de Silenciamento de Genes
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Masculino
Camundongos Nus
Meia-Idade
Proteínas Oncogênicas/genética
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Nck protein); 0 (Oncogene Proteins); 0 (STAT3 Transcription Factor); EC 2.7.10.2 (Focal Adhesion Kinase 2); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28455143
[Au] Autor:Li H; Li B; Larose L
[Ad] Endereço:Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada; The Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
[Ti] Título:IRE1α links Nck1 deficiency to attenuated PTP1B expression in HepG2 cells.
[So] Source:Cell Signal;36:79-90, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine phosphatase superfamily, plays a key role in regulating intracellular signaling from various receptor and non-receptor protein tyrosine kinases. Previously, we reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells enhances basal and growth factor-induced activation of the PI3K-Akt pathway through attenuating PTP1B expression. However, the underlying mechanism by which Nck1 depletion represses PTP1B expression remains unclear. In this study, we found that silencing Nck1 attenuates PTP1B expression in HepG2 cells through down-regulation of IRE1α. Indeed, we show that silencing Nck1 in HepG2 cells leads to decreased IRE1α expression and signaling. Accordingly, IRE1α depletion using siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor-induced Akt activation, reproducing the effects of silencing Nck1 on activation of this pathway. In addition, depletion of IRE1α also leads to reduced PTP1B expression, which was rescued by ectopic expression of IRE1α in Nck1-depleted cells. Mechanistically, we found that silencing either Nck1 or IRE1α in HepG2 cells decreases PTP1B mRNA levels and stability. However, despite miR-122 levels, a miRNA targeting PTP1B 3' UTR and inducing PTP1B mRNA degradation in HepG2 cells, are increased in both Nck1- and IRE1α-depleted HepG2 cells, a miR-122 antagomir did not rescue PTP1B expression in these cells. Overall, this study highlights an important role for Nck1 in fine-tuning IRE1α expression and signaling that regulate PTP1B expression and subsequent activation of the PI3K-Akt pathway in HepG2 cells.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/deficiência
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Endorribonucleases/metabolismo
Proteínas Oncogênicas/deficiência
Proteínas Oncogênicas/metabolismo
Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/química
Animais
Ativação Enzimática/efeitos dos fármacos
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Inativação Gênica/efeitos dos fármacos
Células HeLa
Células Hep G2
Seres Humanos
Camundongos
MicroRNAs/metabolismo
Proteínas Oncogênicas/química
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação/efeitos dos fármacos
Ligação Proteica/efeitos dos fármacos
Domínios Proteicos
Proteína Tirosina Fosfatase não Receptora Tipo 1/genética
Proteínas Proto-Oncogênicas c-akt/metabolismo
Estabilidade de RNA/efeitos dos fármacos
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Transdução de Sinais/efeitos dos fármacos
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (MIRN122 microRNA, human); 0 (MicroRNAs); 0 (Nck protein); 0 (Oncogene Proteins); 0 (RNA, Messenger); 67526-95-8 (Thapsigargin); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (ERN1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.- (Endoribonucleases); EC 3.1.3.48 (PTPN1 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:29305865
[Au] Autor:Yin K; Dang S; Cui L; Fan X; Xie R; Qu J; Shang M; Chen J
[Ad] Endereço:Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
[Ti] Título:Netrin-1 promotes metastasis of gastric cancer by regulating YAP activity.
[So] Source:Biochem Biophys Res Commun;496(1):76-82, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Yes-associated protein (YAP) is a major downstream molecular of the Hippo pathway, which plays important role in cancer development. Netrin-1 conveys oncogenic activity in many types of malignant tumors. However, the downstream signaling of netrin-1 mediating its oncogenic effects in gastric cancer (GC) is not well defined. Here, we aim to investigate the role of netrin-1 in metastasis potential of GC by regulating YAP. In this study, we showed that netrin-1 inhibition significantly decreased migration and invasion abilities of GC cells, while netrin-1 overexpression effectively reversed this effect. We also demonstrated that netrin-1 upregulated YAP expression via its transmembrane receptor neogenin. Furthermore, our in vitro and in vivo results showed that the effect of netrin-1 on GC cells migration and invasion abilities was regulated by YAP. Collectively, our results defined netrin-1 as a positive regulator of malignant tumor metastasis in GC by activating the YAP signaling, with potential implications for new approaches to GC therapy.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Regulação Neoplásica da Expressão Gênica
Netrina-1/metabolismo
Fosfoproteínas/metabolismo
Neoplasias Gástricas/metabolismo
Neoplasias Gástricas/patologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Invasividade Neoplásica
Metástase Neoplásica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (NTN1 protein, human); 0 (Phosphoproteins); 0 (YAP1 (Yes-associated) protein, human); 158651-98-0 (Netrin-1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


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[PMID]:28460446
[Au] Autor:Kapil S; Sharma BK; Patil M; Elattar S; Yuan J; Hou SX; Kolhe R; Satyanarayana A
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Molecular Oncology & Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
[Ti] Título:The cell polarity protein Scrib functions as a tumor suppressor in liver cancer.
[So] Source:Oncotarget;8(16):26515-26531, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Scrib is a membrane protein that is involved in the maintenance of apical-basal cell polarity of the epithelial tissues. However, Scrib has also been shown to be mislocalized to the cytoplasm in breast and prostate cancer. Here, for the first time, we report that Scrib not only translocates to the cytoplasm but also to the nucleus in hepatocellular carcinoma (HCC) cells, and in mouse and human liver tumor samples. We demonstrate that Scrib overexpression suppresses the growth of HCC cells in vitro, and Scrib deficiency enhances liver tumor growth in vivo. At the molecular level, we have identified the existence of a positive feed-back loop between Yap1 and c-Myc in HCC cells, which Scrib disrupts by simultaneously regulating the MAPK/ERK and Hippo signaling pathways. Overall, Scrib inhibits liver cancer cell proliferation by suppressing the expression of three oncogenes, Yap1, c-Myc and cyclin D1, thereby functioning as a tumor suppressor in liver cancer.
[Mh] Termos MeSH primário: Neoplasias Hepáticas/metabolismo
Proteínas de Membrana/metabolismo
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Proteínas Adaptadoras de Transdução de Sinal/genética
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Animais
Ciclo Celular/genética
Linhagem Celular Tumoral
Proliferação Celular
Transformação Celular Neoplásica/induzido quimicamente
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/metabolismo
Ciclina D1/genética
Ciclina D1/metabolismo
Modelos Animais de Doenças
Expressão Gênica
Xenoenxertos
Seres Humanos
Neoplasias Hepáticas/genética
Sistema de Sinalização das MAP Quinases
Proteínas de Membrana/genética
Camundongos
Fosfoproteínas/genética
Fosfoproteínas/metabolismo
Ligação Proteica
Transporte Proteico
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Proto-Oncogênicas c-myc/genética
Proteínas Proto-Oncogênicas c-myc/metabolismo
Transdução de Sinais
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Membrane Proteins); 0 (Phosphoproteins); 0 (Proto-Oncogene Proteins c-myc); 0 (SCRIB protein, human); 0 (Tumor Suppressor Proteins); 0 (YAP1 (Yes-associated) protein, human); 136601-57-5 (Cyclin D1); EC 2.7.11.1 (Hippo protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15713


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[PMID]:28451636
[Au] Autor:Erb M; Lee B; Yeon Seo S; Lee JW; Lee S; Lee SK
[Ad] Endereço:Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239.
[Ti] Título:The Isl1-Lhx3 Complex Promotes Motor Neuron Specification by Activating Transcriptional Pathways that Enhance Its Own Expression and Formation.
[So] Source:eNeuro;4(2), 2017 Mar-Apr.
[Is] ISSN:2373-2822
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Motor neuron (MN) progenitor cells rapidly induce high expression of the transcription factors Islet-1 (Isl1), LIM-homeobox 3 (Lhx3), and the transcriptional regulator LMO4, as they differentiate. While these factors are critical for MN specification, the mechanisms regulating their precise temporal and spatial expression patterns are not well characterized. Isl1 and Lhx3 form the Isl1-Lhx3 complex, which induces the transcription of genes critical for MN specification and maturation. Here, we report that , , and are direct target genes of the Isl1-Lhx3 complex. Our results show that specific genomic loci associated with these genes recruit the Isl1-Lhx3 complex to activate the transcription of , , and in embryonic MNs of chick and mouse. These findings support a model in which the Isl1-Lhx3 complex amplifies its own expression through a potent autoregulatory feedback loop and simultaneously enhances the transcription of . LMO4 blocks the formation of the V2 interneuron-specifying Lhx3 complex. In developing MNs, this action inhibits the expression of V2 interneuron genes and increases the pool of unbound Lhx3 available to incorporate into the Isl1-Lhx3 complex. Identifying the pathways that regulate the expression of these key factors provides important insights into the genetic strategies utilized to promote MN differentiation and maturation.
[Mh] Termos MeSH primário: Proteínas com Homeodomínio LIM/metabolismo
Neurônios Motores/metabolismo
Fatores de Transcrição/metabolismo
Ativação Transcricional
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Animais
Proteínas Aviárias/metabolismo
Embrião de Galinha
Proteínas de Ligação a DNA/metabolismo
Proteínas com Domínio LIM/metabolismo
Camundongos
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Avian Proteins); 0 (DNA-Binding Proteins); 0 (LIM Domain Proteins); 0 (LIM-Homeodomain Proteins); 0 (Lhx3 protein); 0 (Lmo4 protein, mouse); 0 (Transcription Factors); 0 (insulin gene enhancer binding protein Isl-1)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29317664
[Au] Autor:Choi HJ; Park A; Kang S; Lee E; Lee TA; Ra EA; Lee J; Lee S; Park B
[Ad] Endereço:Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, South Korea.
[Ti] Título:Human cytomegalovirus-encoded US9 targets MAVS and STING signaling to evade type I interferon immune responses.
[So] Source:Nat Commun;9(1):125, 2018 01 09.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanisms that target both the innate and adaptive immune responses. However, how HCMV encoded proteins are involved in this immune escape is not clear. Here, we show that HCMV glycoprotein US9 inhibits the IFN-ß response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria. Furthermore, US9 disrupts STING oligomerization and STING-TBK1 association through competitive interaction. Intriguingly, US9 blocks interferon regulatory factor 3 (IRF3) nuclear translocation and its cytoplasmic domain is essential for inhibiting IRF3 activation. Mutant HCMV lacking US7-16 is impaired in antagonism of MAVS/STING-mediated IFN-ß expression, an effect that is reversible by the introduction of US9. Our findings indicate that HCMV US9 is an antagonist of IFN signaling to persistently evade host innate antiviral responses.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/imunologia
Interferon Tipo I/imunologia
Glicoproteínas de Membrana/imunologia
Proteínas de Membrana/imunologia
Proteínas Virais/imunologia
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Células Cultivadas
Células HEK293
Células HeLa
Interações Hospedeiro-Patógeno/imunologia
Seres Humanos
Evasão da Resposta Imune/imunologia
Fator Regulador 3 de Interferon/imunologia
Fator Regulador 3 de Interferon/metabolismo
Interferon Tipo I/metabolismo
Glicoproteínas de Membrana/fisiologia
Proteínas de Membrana/metabolismo
Mitocôndrias/imunologia
Mitocôndrias/metabolismo
Mitocôndrias/virologia
Transdução de Sinais/imunologia
Células U937
Proteínas Virais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (IRF3 protein, human); 0 (Interferon Regulatory Factor-3); 0 (Interferon Type I); 0 (MPYS protein, human); 0 (Membrane Glycoproteins); 0 (Membrane Proteins); 0 (US9 protein, Human herpesvirus 5); 0 (VISA protein, human); 0 (Viral Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02624-8


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[PMID]:27771154
[Au] Autor:Barbieri M; Marfella R; Esposito A; Rizzo MR; Angellotti E; Mauro C; Siniscalchi M; Chirico F; Caiazzo P; Furbatto F; Bellis A; D'Onofrio N; Vitiello M; Ferraraccio F; Paolisso G; Balestrieri ML
[Ad] Endereço:Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Piazza Miraglia 2, 80138, Naples, Italy. Electronic address: michelangela.barbieri@unina2.it.
[Ti] Título:Incretin treatment and atherosclerotic plaque stability: Role of adiponectin/APPL1 signaling pathway.
[So] Source:J Diabetes Complications;31(2):295-303, 2017 Feb.
[Is] ISSN:1873-460X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated. METHODS: The effect of incretin therapy in the regulation of adiponectin/APPL1 signaling was evaluated both on carotid plaques of asymptomatic diabetic (n=71) and non-diabetic patients (n=52), and through in vitro experiments on endothelial cell (EC). RESULTS: Atherosclerotic plaques of T2DM patients showed lower adiponectin and APPL1 levels compared with non-diabetic patients, along with higher oxidative stress, tumor necrosis factor-α (TNF-α), vimentin, and matrix metalloproteinase-9 (MMP-9) levels. Among T2DM subjects, current incretin-users presented higher APPL1 and adiponectin content compared with never incretin-users. Similarly, in vitro observations on endothelial cells co-treated with high-glucose (25mM) and GLP-1 (100nM) showed a greater APPL1 protein expression compared with high-glucose treatment alone. CONCLUSIONS: Our findings suggest a potential role of adiponectin/APPL1 signaling in mediating the effect of incretin in the prevention of atherosclerosis progression or plaque vulnerability in T2DM.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/agonistas
Adiponectina/metabolismo
Diabetes Mellitus Tipo 2/tratamento farmacológico
Angiopatias Diabéticas/prevenção & controle
Incretinas/uso terapêutico
Placa Aterosclerótica/prevenção & controle
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Idoso
Anti-Inflamatórios não Esteroides/farmacologia
Anti-Inflamatórios não Esteroides/uso terapêutico
Antioxidantes/farmacologia
Antioxidantes/uso terapêutico
Estenose das Carótidas/complicações
Estenose das Carótidas/epidemiologia
Estenose das Carótidas/prevenção & controle
Estenose das Carótidas/cirurgia
Células Cultivadas
Diabetes Mellitus Tipo 2/complicações
Diabetes Mellitus Tipo 2/metabolismo
Diabetes Mellitus Tipo 2/patologia
Angiopatias Diabéticas/epidemiologia
Angiopatias Diabéticas/patologia
Angiopatias Diabéticas/cirurgia
Endarterectomia das Carótidas
Endotélio Vascular/efeitos dos fármacos
Endotélio Vascular/imunologia
Endotélio Vascular/metabolismo
Endotélio Vascular/patologia
Feminino
Peptídeo 1 Semelhante ao Glucagon/metabolismo
Seres Humanos
Incretinas/farmacologia
Itália/epidemiologia
Masculino
Estresse Oxidativo/efeitos dos fármacos
Placa Aterosclerótica/complicações
Placa Aterosclerótica/epidemiologia
Placa Aterosclerótica/patologia
Fatores de Risco
Prevenção Secundária
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ADIPOQ protein, human); 0 (APPL1 protein, human); 0 (Adaptor Proteins, Signal Transducing); 0 (Adiponectin); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antioxidants); 0 (Incretins); 89750-14-1 (Glucagon-Like Peptide 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE



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