ADAM10 and ADAM17: Novel Players in Retinoblastoma Carcinogenesis
| Autor: | Dario Van Meenen, Annika Doege, Emily Alefeld, André Haase, Manfred Beier, Tobias Kiefer, Eva Biewald, Klaus Metz, Oliver Dräger, Maike Anna Busch, Nicole Dünker |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Disintegrins
Retinal Neoplasms Medizin Neural Cell Adhesion Molecule L1 ADAM17 Protein Catalysis retinoblastoma Inorganic Chemistry ADAM10 Protein Serine Humans ddc:610 Physical and Theoretical Chemistry Molecular Biology Spectroscopy Medizinische Fakultät » Universitätsklinikum Essen » Center for Translational and Behavioral Neuroscience ADAM17 Organic Chemistry Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Augenheilkunde Membrane Proteins ADAM10 General Medicine Medizinische Fakultät » Universitätsklinikum Essen » Institut für Pathologie Medizinische Fakultät » Universitätsklinikum Essen » Institut für Anatomie Computer Science Applications CAM assay MicroRNAs tumorigenesis L1CAM retinoblastoma -- ADAM10 -- ADAM17 -- L1CAM -- CAM assay -- carcinogenesis -- tumorigenesis carcinogenesis Amyloid Precursor Protein Secretases Proto-Oncogene Proteins c-akt |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 20; Pages: 12621 |
| Popis: | OA Förderung 2022 A disintegrin and metalloproteinase (ADAM) family proteins, acting as sheddases, are important factors in a number of pathologies, including cancer, and have been suggested as promising therapeutic targets. The study presented focuses on the involvement of ADAM10 and ADAM17 in retinoblastoma (RB), the most common malignant intraocular childhood tumor. A significant correlation between ADAM17 expression levels and RB laterality and RB staging was observed. Levels of ADAM10 or ADAM17 regulating miRNAs miR-145, -152, and -365 were significantly downregulated in RB cell lines, and reduced miR levels with simultaneously upregulated ADAM10 and ADAM17 expression were found in RB patients. The involvement of both ADAMs analyzed in ectodomain shedding of the neuronal cell adhesion molecule L1 (L1CAM), shown to induce pro-tumorigenic effects in RB, was confirmed. Lentiviral ADAM10 and ADAM17 single or ADAM10/17 double knockdown (KD) induced caspase-dependent apoptosis and reduced cell viability, proliferation, growth, and colony formation capacity of RB cells. Moreover, differential phosphorylation of the serine/threonine kinase AKT was observed following ADAM17 KD in RB cells. Chicken chorioallantoic membrane (CAM) assays revealed that ADAM17 and ADAM10/17 depletion decreases the tumorigenic and migration potential of RB cells in vivo. Thus, ADAMs are potential novel targets for future therapeutic RB approaches. |
| Databáze: | OpenAIRE |
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