Browsing by Subject "ADAM10"

Now showing 1 - 4 of 4
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    MITF induces escape from innate immunity in melanoma
    (BMC, 2021) Martí-Díaz, Román; González-Guerrero, Rebeca; Martínez-Barba, Enrique; Piñero-Madrona, Antonio; Cabezas-Herrera, Juan; Goding, Colin R.; Montenegro Arce, María Fernanda; Hernández Caselles, Trinidad; Rodríguez López, José Neptuno; Sánchez del Campo Ferrer, Luis; Bioquímica y Biología Molecular B e Inmunología
    Background: The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods: By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results: Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion: Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.
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    MITF induces escape from innate immunity in melanoma
    (Springer Nature, 2021-03-31) Martí Díaz, Román; González Guerrero, Rebeca; Martínez Barba, Enrique; Piñero Madrona, Antonio; Cabezas Herrera, Juan; Goding, Colin; Montenegro Arce, María Fernanda; Hernández Caselles, Trinidad; Rodríguez López, José Neptuno; Sánchez del Campo Ferrer, Luis; Bioquímica y Biología Molecular A
    Background The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies. Background
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    N-Cadherin, ADAM-10 and Aquaporin 1 expression in lung tissue exposed to fluoroedenite fibers: an immunohistochemical study
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Musumeci, Giuseppe; Loreto, Carla; Szychlinska, Marta Anna; Imbesi, Rosa; Rapisarda, Venerando; Aiello, Flavia Concetta; Castorina, Sergio; Castrogiovanni, Paola
    Fluoro-edenite (FE) fibers are similar to other amphibole asbestos fibers. The scientific relevance of FE is due to its ability to lead to chronic inflammation and carcinogenesis in lung tissue shown after its inhalation. These fibers stimulate aberrant host cell proliferation and induce the release of cytokines, growth factors, reactive oxygen and nitrite species, which results in DNA damage. In previous studies, we showed that FE induces functional modifications in sheep and human lung fibroblasts and alveolar epithelial cells, where the overexpression of several molecules probably involved in pathological cellular mechanisms induced by FE exposition have been detected. However, the mechanisms of cellular and molecular toxicity and the cellular response to FE fibers are still not well known. N-cadherin, ADAM-10 and AQP1 are molecules involved in carcinogenesis and in inflammatory process. In this study we analyzed, through immunohistochemistry, their expression in the lung tissue of sheep exposed to FE. Our results showed different patterns of immunolabeling for N-cadherin, ADAM-10 and AQP1. N-cadherin and ADAM-10 were more expressed in FE exposed lung tissue, when compared with the control. On the contrary, AQP1 was more expressed in non exposed lung tissue. These results suggest that NCadherin, ADAM-10 and AQP1 are probably involved in different pathological processes induced by FE fiber exposition. The aim of the study was to better understand the mechanisms of cellular and molecular toxicity and of cellular response to FE fibers in order to identify, in the future, a possible therapeutic intervention in cases of FE-associated pathogenesis.
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    NCK1-AS1 promotes the proliferation, migration, invasion, and EMT of non-small cell lung cancer by regulating the miR-361-5p/ADAM10 axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wu, Bingchen; Wang, Zizong; Xu, Hanlin; Chu, Xiangyang; Jiang, Qiwen
    Lung cancer, one of the most frequently diagnosed cancers, causes a huge number of mortalities globally. Among lung cancers, non-small cell lung cancer (NSCLC) is the most recorded. Despite accumulating research, the molecular basis of NSCLC progression remains poorly known. Therefore, we aim to assess the function of NCK1-AS1 in NSCLC and elucidate the molecular mechanism. Firstly, we quantified the NCK1-AS1 level in tumors and adjacent healthy tissues. NCK1-AS1 was significantly upregulated in NSCLC tumors, which was associated with poor prognosis in patients. Silencing NCK1-AS1 significantly inhibited the proliferation, migration, and invasion, as well as the EMT of NSCLC cell lines. Starbase bioinformatic prediction revealed that NCK1AS1 targets miR-361-5p which acts to regulate ADAM10 gene expression. Our result showed that NCK1-AS1 upregulation markedly reduced miR-361-5p mRNA expression, while increasing ADAM10 expression. For the first time, we demonstrated that NCK1-AS1 regulates the miR-361-5p/ADAM10 axis, thereby promoting NSCLC progression. NCK1-AS1 might be developed as a therapeutic target for treating NSCLC.