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Pesquisa : D08.811.913.696.620.682.725.800.630 [Categoria DeCS]
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[PMID]:28733485
[Au] Autor:Ghosh D; Brown SL; Stumhofer JS
[Ad] Endereço:Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205.
[Ti] Título:IL-17 Promotes Differentiation of Splenic LSK Lymphoid Progenitors into B Cells following Infection.
[So] Source:J Immunol;199(5):1783-1795, 2017 Sep 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lineage Sca-1 c-Kit (LSK ) cells are a lymphoid progenitor population that expands in the spleen and preferentially differentiates into mature B cells in response to infection in mice. Furthermore, LSK derived B cells can subsequently contribute to the ongoing immune response through the generation of parasite-specific Ab-secreting cells, as well as germinal center and memory B cells. However, the factors that promote their differentiation into B cells in the spleen postinfection are not defined. In this article, we show that LSK cells produce the cytokine IL-17 in response to infection. Using mice, IL-17R signaling in cells other than LSK cells was found to support their differentiation into B cells. Moreover, primary splenic stromal cells grown in the presence of IL-17 enhanced the production of CXCL12, a chemokine associated with B cell development in the bone marrow, by a population of IL-17RA-expressing podoplanin CD31 stromal cells, a profile associated with fibroblastic reticular cells. Subsequent blockade of CXCL12 in vitro reduced differentiation of LSK cells into B cells, supporting a direct role for this chemokine in this process. Immunofluorescence indicated that podoplanin stromal cells in the red pulp were the primary producers of CXCL12 after infection. Furthermore, podoplanin staining on stromal cells was more diffuse, and CXCL12 staining was dramatically reduced in mice postinfection. Together, these results identify a distinct pathway that supports lymphoid development in the spleen during acute infection.
[Mh] Termos MeSH primário: Células Produtoras de Anticorpos/fisiologia
Linfócitos B/fisiologia
Interleucina-17/metabolismo
Células Progenitoras Linfoides/fisiologia
Malária/imunologia
Plasmodium yoelii/imunologia
Baço/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antiprotozoários/metabolismo
Células Produtoras de Anticorpos/parasitologia
Linfócitos B/parasitologia
Diferenciação Celular
Células Cultivadas
Quimiocina CXCL12/metabolismo
Feminino
Seres Humanos
Memória Imunológica
Células Progenitoras Linfoides/parasitologia
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Camundongos Knockout
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
Receptores de Interleucina-17/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Chemokine CXCL12); 0 (Il17r protein, mouse); 0 (Interleukin-17); 0 (Receptors, Interleukin-17); EC 2.7.1.- (Matk protein, mouse); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170723
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601972


  2 / 2158 MEDLINE  
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[PMID]:28442265
[Au] Autor:Lan T; Wang H; Zhang Z; Zhang M; Qu Y; Zhao Z; Fan X; Zhan Q; Song Y; Yu C
[Ad] Endereço:Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China; State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
[Ti] Título:Downregulation of ß-arrestin 1 suppresses glioblastoma cell malignant progression vis inhibition of Src signaling.
[So] Source:Exp Cell Res;357(1):51-58, 2017 Aug 01.
[Is] ISSN:1090-2422
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glioblastoma multiforme (GBM) is one of the most common brain malignancies worldwide and is typically associated with a dismal prognosis, yet the mechanisms underlying its aggressiveness remain unclear. Here, we revealed that ß-arrestin 1 was overexpressed in GBM and contributed to poorer outcome. Knockdown of ß-arrestin 1 suppressed the proliferation, invasiveness and glycolysis of GBM cells, and also enhanced temozolomide efficacy. Further, we discovered that knockdown of ß-arrestin 1 decreased the activity of Src, and suppression of Src signaling was critically involved in ß-arrestin 1 silencing-mediated suppression of GBM malignancies. Finally, we investigated the effect of ß-arrestin 1 knockdown on the tumor growth and survival of xenograft models, and found that shß-arrestin 1 apparently inhibited GBM growth in vivo and resulted in better survival of mice. Taken together, our findings suggest that knockdown of ß-arrestin 1 can suppress GBM cell proliferation, invasion and glycolysis by inhibiting Src signaling. Thus, targeting ß-arrestin 1 may be a potential therapeutic strategy for GBM treatment.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/metabolismo
Glioblastoma/metabolismo
Transdução de Sinais
beta-Arrestina 1/metabolismo
[Mh] Termos MeSH secundário: Animais
Neoplasias Encefálicas/tratamento farmacológico
Neoplasias Encefálicas/patologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Dacarbazina/análogos & derivados
Dacarbazina/farmacologia
Progressão da Doença
Regulação para Baixo/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Glioblastoma/tratamento farmacológico
Glioblastoma/patologia
Seres Humanos
Camundongos
Invasividade Neoplásica/patologia
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ARRB1 protein, human); 0 (Arrb1 protein, mouse); 0 (beta-Arrestin 1); 7GR28W0FJI (Dacarbazine); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src)); YF1K15M17Y (temozolomide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE


  3 / 2158 MEDLINE  
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[PMID]:28423613
[Au] Autor:Li R; Yanjiao G; Wubin H; Yue W; Jianhua H; Huachuan Z; Rongjian S; Zhidong L
[Ad] Endereço:Department of Cell Biology, College of Basic Medicine, Jinzhou Medical University, Jinzhou, China.
[Ti] Título:Secreted GRP78 activates EGFR-SRC-STAT3 signaling and confers the resistance to sorafeinib in HCC cells.
[So] Source:Oncotarget;8(12):19354-19364, 2017 Mar 21.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acquired resistance is a common phenomenon for HCC patients who undergone sorafenib treatment, however the mechanism by which acquired resistance develops remains elusive. In this study, we found that GRP78 could be detected in the serum samples of HCC patients and the conditional medium of multiple HCC cell lines, suggesting that GRP78 is secreted by HCC cells. Further studies showed that secreted GRP78 facilitated the proliferation and inhibited the apoptosis induced by sorafenib both in HCC cell lines and in tumor xenografts. We further found that secreted GRP78 could interact physically with EGFR, therefore activates EGFR signaling pathway. knockdown of EGFR decreased secreted GRP78 induced phosphorylation of SRC and STAT3. By contrast, overexpression of EGFR further enhanced the phosphorylation of SRC and STAT3 induced by secreted GRP78, suggesting the critical role of EGFR in secreted GRP78 conferred resistance to sorafeinib. Moreover, inhibition of SRC by PP2 antagonized the resistance to sorafenib and inhibited the activation of STAT3 conferred by secreted GRP78. Taken together, our results showed that secreted GRP78 could interact with EGFR, activate EGFR-SRC-STAT3 signaling, conferring the resistance to sorafenib.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/patologia
Resistência a Medicamentos Antineoplásicos
Proteínas de Choque Térmico/metabolismo
Niacinamida/análogos & derivados
Compostos de Fenilureia/farmacologia
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
Receptor do Fator de Crescimento Epidérmico/metabolismo
Fator de Transcrição STAT3/metabolismo
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Biomarcadores Tumorais/genética
Biomarcadores Tumorais/metabolismo
Carcinoma Hepatocelular/tratamento farmacológico
Carcinoma Hepatocelular/metabolismo
Proliferação Celular/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Proteínas de Choque Térmico/genética
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Camundongos
Camundongos Nus
Niacinamida/farmacologia
Fosforilação/efeitos dos fármacos
Proteínas Proto-Oncogênicas pp60(c-src)/genética
Receptor do Fator de Crescimento Epidérmico/genética
Fator de Transcrição STAT3/genética
Transdução de Sinais/efeitos dos fármacos
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (Heat-Shock Proteins); 0 (Phenylurea Compounds); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 0 (molecular chaperone GRP78); 25X51I8RD4 (Niacinamide); 9ZOQ3TZI87 (sorafenib); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15223


  4 / 2158 MEDLINE  
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[PMID]:28249041
[Au] Autor:Martín R; Cordova C; Gutiérrez B; Hernández M; Nieto ML
[Ad] Endereço:Instituto de Biología y Genética Molecular (IBGM), CSIC-UVa, Valladolid, Spain.
[Ti] Título:A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells.
[So] Source:PLoS One;12(3):e0170675, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA). Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications.
[Mh] Termos MeSH primário: Astrocitoma/metabolismo
Movimento Celular
Proliferação Celular
Regulação Enzimológica da Expressão Gênica
Regulação Neoplásica da Expressão Gênica
Leptina/metabolismo
Sistema de Sinalização das MAP Quinases
Fosfolipases A2 Secretórias/biossíntese
Ativação Transcricional
[Mh] Termos MeSH secundário: Animais
Astrocitoma/genética
Astrocitoma/patologia
Linhagem Celular Tumoral
MAP Quinases Reguladas por Sinal Extracelular/genética
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Seres Humanos
Leptina/genética
Leptina/farmacologia
Camundongos
Fosfolipases A2 Secretórias/genética
Proteínas Proto-Oncogênicas c-akt/genética
Proteínas Proto-Oncogênicas c-akt/metabolismo
Proteínas Proto-Oncogênicas pp60(c-src)/genética
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
Receptor do Fator de Crescimento Epidérmico/genética
Receptor do Fator de Crescimento Epidérmico/metabolismo
Receptores para Leptina/biossíntese
Receptores para Leptina/genética
Proteínas Quinases S6 Ribossômicas 70-kDa/genética
Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo
Serina-Treonina Quinases TOR/genética
Serina-Treonina Quinases TOR/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Leptin); 0 (Receptors, Leptin); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src)); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 3.1.1.4 (Phospholipases A2, Secretory)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170302
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170675


  5 / 2158 MEDLINE  
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[PMID]:28050799
[Au] Autor:Flamini MI; Uzair ID; Pennacchio GE; Neira FJ; Mondaca JM; Cuello-Carrión FD; Jahn GA; Simoncini T; Sanchez AM
[Ad] Endereço:Laboratorio de Biología Tumoral. Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.
[Ti] Título:Thyroid Hormone Controls Breast Cancer Cell Movement via Integrin αV/ß3/SRC/FAK/PI3-Kinases.
[So] Source:Horm Cancer;8(1):16-27, 2017 Feb.
[Is] ISSN:1868-8500
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Thyroid hormones (TH) play a fundamental role in diverse processes, including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are driven by actin remodeling and stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that promotes cell migration and invasion through the control of focal adhesion turnover. In this work, we demonstrate that the thyroid hormone triiodothyronine (T3) regulates actin remodeling and cell movement in breast cancer T-47D cells through the recruitment of FAK. T3 controls FAK phosphorylation and translocation at sites where focal adhesion complexes are assembled. This process is triggered via rapid signaling to integrin αV/ß3, Src, phosphatidylinositol 3-OH kinase (PI3K), and FAK. In addition, we established a cellular model with different concentration of T3 levels: normal, absence, and excess in T-47D breast cancer cells. We found that the expression of Src, FAK, and PI3K remained at normal levels in the excess of T3 model, while it was significantly reduced in the absence model. In conclusion, these results suggest a novel role for T3 as an important modulator of cell migration, providing a starting point for the development of new therapeutic strategies for breast cancer treatment.
[Mh] Termos MeSH primário: Citoesqueleto de Actina/metabolismo
Neoplasias da Mama/enzimologia
Neoplasias da Mama/patologia
Quinase 1 de Adesão Focal/metabolismo
Tri-Iodotironina/metabolismo
[Mh] Termos MeSH secundário: Adesão Celular
Linhagem Celular Tumoral
Movimento Celular
Feminino
Adesões Focais/metabolismo
Seres Humanos
Integrina alfaVbeta3/metabolismo
Invasividade Neoplásica
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação
Transporte Proteico
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin alphaVbeta3); 06LU7C9H1V (Triiodothyronine); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.2 (Focal Adhesion Kinase 1); EC 2.7.10.2 (PTK2 protein, human); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170105
[St] Status:MEDLINE
[do] DOI:10.1007/s12672-016-0280-3


  6 / 2158 MEDLINE  
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[PMID]:27980063
[Au] Autor:Nagarajan S; Bedi U; Budida A; Hamdan FH; Mishra VK; Najafova Z; Xie W; Alawi M; Indenbirken D; Knapp S; Chiang CM; Grundhoff A; Kari V; Scheel CH; Wegwitz F; Johnsen SA
[Ad] Endereço:Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences, University Medical Center Göttingen, 37077 Göttingen, Germany.
[Ti] Título:BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells.
[So] Source:Nucleic Acids Res;45(6):3130-3145, 2017 Apr 07.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bromodomain-containing protein 4 (BRD4) is a member of the bromo- and extraterminal (BET) domain-containing family of epigenetic readers which is under intensive investigation as a target for anti-tumor therapy. BRD4 plays a central role in promoting the expression of select subsets of genes including many driven by oncogenic transcription factors and signaling pathways. However, the role of BRD4 and the effects of BET inhibitors in non-transformed cells remain mostly unclear. We demonstrate that BRD4 is required for the maintenance of a basal epithelial phenotype by regulating the expression of epithelial-specific genes including TP63 and Grainy Head-like transcription factor-3 (GRHL3) in non-transformed basal-like mammary epithelial cells. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription. Motif analyses of cell context-specific BRD4-enriched regions predicted the involvement of FOXO transcription factors. Consistently, activation of FOXO1 function via inhibition of EGFR-AKT signaling promoted the expression of TP63 and GRHL3. Moreover, activation of Src kinase signaling and FOXO1 inhibition decreased the expression of FOXO/BRD4 target genes. Together, our findings support a function for BRD4 in promoting basal mammary cell epithelial differentiation, at least in part, by regulating FOXO factor function on enhancers to activate TP63 and GRHL3 expression.
[Mh] Termos MeSH primário: Mama/metabolismo
Proteínas de Ligação a DNA/genética
Células Epiteliais/metabolismo
Regulação da Expressão Gênica
Proteínas Nucleares/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Mama/citologia
Linhagem Celular
Proteínas de Ligação a DNA/biossíntese
Elementos Facilitadores Genéticos
Fatores de Transcrição Forkhead/metabolismo
Seres Humanos
Proteínas Proto-Oncogênicas c-akt/metabolismo
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
RNA Polimerase II/metabolismo
Transdução de Sinais
Fatores de Transcrição/biossíntese
Transcrição Genética
Proteínas Supressoras de Tumor/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BRD4 protein, human); 0 (DNA-Binding Proteins); 0 (Forkhead Transcription Factors); 0 (GRHL3 protein, human); 0 (Nuclear Proteins); 0 (TP63 protein, human); 0 (Transcription Factors); 0 (Tumor Suppressor Proteins); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src)); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.7.- (RNA Polymerase II)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161217
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkw1276


  7 / 2158 MEDLINE  
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[PMID]:27819680
[Au] Autor:Urbinati C; Grillo E; Chiodelli P; Tobia C; Caccuri F; Fiorentini S; David G; Rusnati M
[Ad] Endereço:Section of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
[Ti] Título:Syndecan-1 increases B-lymphoid cell extravasation in response to HIV-1 Tat via α ß /pp60src/pp125FAK pathway.
[So] Source:Oncogene;36(18):2609-2618, 2017 May 04.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Syndecan-1 is a heparan sulfate proteoglycan (HSPG) commonly upregulated in AIDS-related B lymphoid malignancies. Tat is the main HIV-1 transactivating factor that has a major role in the pathogenesis of AIDS-related lymphomas (ARL) by engaging heparan sulfate proteoglycans (HSPGs), chemokine receptors and integrins at the lymphoid cell (LC) surface. Here B-lymphoid Namalwa cell clones that do not express or overexpress syndecan-1 (EV-Ncs and SYN-Ncs, respectively) were compared for their responsiveness with Tat: in the absence of syndecan-1, Tat induces a limited EV-Nc migration via C-X-C motif chemokine receptor 4 (CXCR4), G-proteins and Rac. Syndecan-1 overexpression increases SYN-Nc responsiveness to Tat and makes this response independent from CXCR4 and G-protein and dependent instead on pp60src phosphorylation. Tat-induced SYN-Nc migration and pp60src phosphorylation require the engagement of α ß integrin and consequent pp125FAK phosphorylation. This complex set of Tat-driven activations is orchestrated by the direct interaction of syndecan-1 with pp60src and its simultaneous coupling with α ß . The Tat/syndecan-1/α ß interplay is retained in vivo and is shared also by other syndecan-1 B-LCs, including BJAB cells, whose responsiveness to Tat is inhibited by syndecan-1 knockdown. In conclusion, overexpression of syndecan-1 confers to B-LCs an increased capacity to migrate in response to Tat, owing to a switch from a CXCR4/G-protein/Rac to a syndecan-1/α ß /pp60src/pp125FAK signal transduction pathway that depends on the formation of a complex in which syndecan-1 interacts with Tat via its HS-chains, with α ß via its core protein ectodomain and with pp60src via its intracellular tail. These findings have implications in ARL progression and may help in identifying new therapeutical targets for the treatment of AIDS-associated neoplasia.
[Mh] Termos MeSH primário: Quinase 1 de Adesão Focal/genética
Integrina alfaVbeta3/genética
Linfócitos/metabolismo
Neoplasias/genética
Sindecana-1/genética
[Mh] Termos MeSH secundário: Adesão Celular/genética
Regulação Neoplásica da Expressão Gênica
HIV-1/genética
Seres Humanos
Linfócitos/patologia
Complexos Multiproteicos/genética
Neoplasias/patologia
Fosforilação
Proteínas Proto-Oncogênicas pp60(c-src)/genética
Receptores CXCR4/genética
Transdução de Sinais/genética
Produtos do Gene tat do Vírus da Imunodeficiência Humana/administração & dosagem
Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CXCR4 protein, human); 0 (Integrin alphaVbeta3); 0 (Multiprotein Complexes); 0 (Receptors, CXCR4); 0 (Syndecan-1); 0 (tat Gene Products, Human Immunodeficiency Virus); EC 2.7.10.2 (Focal Adhesion Kinase 1); EC 2.7.10.2 (PTK2 protein, human); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161108
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2016.420


  8 / 2158 MEDLINE  
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[PMID]:27819673
[Au] Autor:Wang L; Ren J; Li G; Moorman JP; Yao ZQ; Ning S
[Ad] Endereço:Division of Infectious Diseases, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
[Ti] Título:LMP1 signaling pathway activates IRF4 in latent EBV infection and a positive circuit between PI3K and Src is required.
[So] Source:Oncogene;36(16):2265-2274, 2017 Apr 20.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Interferon (IFN) regulatory factors (IRFs) have crucial roles in immune regulation and oncogenesis. We have recently shown that IRF4 is activated through c-Src-mediated tyrosine phosphorylation in virus-transformed cells. However, the intracellular signaling pathway triggering Src activation of IRF4 remains unknown. In this study, we provide evidence that Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) promotes IRF4 phosphorylation and markedly stimulates IRF4 transcriptional activity, and that Src mediates LMP1 activation of IRF4. As to more precise mechanism, we show that LMP1 physically interacts with c-Src, and the phosphatidylinositol 3 kinase (PI3K) subunit P85 mediates their interaction. Depletion of P85 by P85-specific short hairpin RNAs disrupts their interaction and diminishes IRF4 phosphorylation in EBV-transformed cells. Furthermore, we show that Src is upstream of PI3K for activation of both IRF4 and Akt. In turn, inhibition of PI3K kinase activity by the PI3K-speicfic inhibitor LY294002 impairs Src activity. Our results show that LMP1 signaling is responsible for IRF4 activation, and further characterize the IRF4 regulatory network that is a promising therapeutic target for specific hematological malignancies.
[Mh] Termos MeSH primário: Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo
Infecções por Vírus Epstein-Barr/metabolismo
Fatores Reguladores de Interferon/metabolismo
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
Proteínas da Matriz Viral/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Células HEK293
Seres Humanos
Fatores Reguladores de Interferon/genética
Fosforilação
Proteínas Proto-Oncogênicas pp60(c-src)/antagonistas & inibidores
Transdução de Sinais
Ativação Transcricional
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (EBV-associated membrane antigen, Epstein-Barr virus); 0 (Interferon Regulatory Factors); 0 (Viral Matrix Proteins); 0 (interferon regulatory factor-4); EC 2.7.1.137 (Class Ia Phosphatidylinositol 3-Kinase); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161108
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2016.380


  9 / 2158 MEDLINE  
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[PMID]:27816970
[Au] Autor:Chen SW; Chou CT; Chang CC; Li YJ; Chen ST; Lin IC; Kok SH; Cheng SJ; Lee JJ; Wu TS; Kuo ML; Lin BR
[Ad] Endereço:Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
[Ti] Título:HMGCS2 enhances invasion and metastasis via direct interaction with PPARα to activate Src signaling in colorectal cancer and oral cancer.
[So] Source:Oncotarget;8(14):22460-22476, 2017 Apr 04.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/metabolismo
Neoplasias Colorretais/metabolismo
Hidroximetilglutaril-CoA Sintase/metabolismo
Mitocôndrias/fisiologia
Neoplasias Bucais/metabolismo
[Mh] Termos MeSH secundário: Animais
Carcinoma de Células Escamosas/diagnóstico
Carcinoma de Células Escamosas/mortalidade
Movimento Celular
Neoplasias Colorretais/diagnóstico
Neoplasias Colorretais/mortalidade
Feminino
Seres Humanos
Hidroximetilglutaril-CoA Sintase/genética
Camundongos
Camundongos SCID
Neoplasias Bucais/diagnóstico
Neoplasias Bucais/mortalidade
PPAR alfa/metabolismo
Prognóstico
Proteínas Proto-Oncogênicas pp60(c-src)/genética
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
RNA Interferente Pequeno/genética
Análise de Sobrevida
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGCS2 protein, human); 0 (PPAR alpha); 0 (RNA, Small Interfering); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.13006


  10 / 2158 MEDLINE  
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[PMID]:27999817
[Au] Autor:Zhao R; Tin L; Zhang Y; Wu Y; Jin Y; Jin X; Zhang F; Li X
[Ad] Endereço:Department of Pathology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
[Ti] Título:EF24 Suppresses Invasion and Migration of Hepatocellular Carcinoma Cells via Inhibiting the Phosphorylation of Src.
[So] Source:Biomed Res Int;2016:8569684, 2016.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Diphenyl difluoroketone (EF24), a curcumin analog, is a promising anticancer compound that exerts its effects by inhibiting cell proliferation and inducing apoptosis. However, the efficacy of EF24 against cancer metastasis, particularly in hepatocellular carcinoma (HCC), remains elusive. In this study, the effect of EF24 on HCCLM-3 and HepG2 cell migration and invasion was detected by wound healing and transwell assay, respectively. The results revealed that EF24 suppressed the migration and invasion of both HCCLM-3 and HepG2 cells. Furthermore, EF24 treatment decreased the formation of filopodia on the cell surface and inhibited the phosphorylation of Src in both cell lines, which may help contribute towards understanding the mechanism underlying the suppressive effect of EF24 on HCC migration and invasion. Additionally, the expression of total- and phosphorylated-Src in primary HCC tissues and their paired lymph node metastatic tissues was detected, and phosphorylated-Src was found to be associated with HCC lymph node metastasis. The results of this study suggest that Src is a novel and promising therapeutic target in HCC and provide evidence to support the hypothesis that EF24 may be a useful therapeutic agent for the treatment of HCC.
[Mh] Termos MeSH primário: Compostos de Benzilideno/farmacologia
Carcinoma Hepatocelular
Movimento Celular/efeitos dos fármacos
Neoplasias Hepáticas
Piperidonas/farmacologia
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/tratamento farmacológico
Carcinoma Hepatocelular/metabolismo
Carcinoma Hepatocelular/patologia
Células Hep G2
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Invasividade Neoplásica
Fosforilação/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3,5-bis(2-fluorobenzylidene)piperidin-4-one); 0 (Benzylidene Compounds); 0 (Piperidones); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170224
[Lr] Data última revisão:
170224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161222
[St] Status:MEDLINE
[do] DOI:10.1155/2016/8569684



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