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Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition
Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation betw...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362532/ https://www.ncbi.nlm.nih.gov/pubmed/22666418 http://dx.doi.org/10.1371/journal.pone.0037941 |
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author | Schmidt, Jennifer Riechers, Alexander Stoll, Raphael Amann, Thomas Fink, Florian Spruss, Thilo Gronwald, Wolfram König, Burkhard Hellerbrand, Claus Bosserhoff, Anja Katrin |
author_facet | Schmidt, Jennifer Riechers, Alexander Stoll, Raphael Amann, Thomas Fink, Florian Spruss, Thilo Gronwald, Wolfram König, Burkhard Hellerbrand, Claus Bosserhoff, Anja Katrin |
author_sort | Schmidt, Jennifer |
collection | PubMed |
description | Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation between dimerization and functional activity. We subsequently identified the dodecapeptide AR71, which prevents MIA dimerization and thereby acts as a MIA inhibitor. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy demonstrated the binding of AR71 to the MIA dimerization domain, in agreement with in vitro and in vivo data revealing reduced cell migration, reduced formation of metastases and increased immune response after AR71 treatment. We believe AR71 is a lead structure for MIA inhibitors. More generally, inhibiting MIA dimerization is a novel therapeutic concept in melanoma therapy. |
format | Online Article Text |
id | pubmed-3362532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33625322012-06-04 Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition Schmidt, Jennifer Riechers, Alexander Stoll, Raphael Amann, Thomas Fink, Florian Spruss, Thilo Gronwald, Wolfram König, Burkhard Hellerbrand, Claus Bosserhoff, Anja Katrin PLoS One Research Article Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation between dimerization and functional activity. We subsequently identified the dodecapeptide AR71, which prevents MIA dimerization and thereby acts as a MIA inhibitor. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy demonstrated the binding of AR71 to the MIA dimerization domain, in agreement with in vitro and in vivo data revealing reduced cell migration, reduced formation of metastases and increased immune response after AR71 treatment. We believe AR71 is a lead structure for MIA inhibitors. More generally, inhibiting MIA dimerization is a novel therapeutic concept in melanoma therapy. Public Library of Science 2012-05-29 /pmc/articles/PMC3362532/ /pubmed/22666418 http://dx.doi.org/10.1371/journal.pone.0037941 Text en Schmidt et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Schmidt, Jennifer Riechers, Alexander Stoll, Raphael Amann, Thomas Fink, Florian Spruss, Thilo Gronwald, Wolfram König, Burkhard Hellerbrand, Claus Bosserhoff, Anja Katrin Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition |
title | Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition |
title_full | Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition |
title_fullStr | Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition |
title_full_unstemmed | Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition |
title_short | Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition |
title_sort | targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (mia) protein inhibition |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362532/ https://www.ncbi.nlm.nih.gov/pubmed/22666418 http://dx.doi.org/10.1371/journal.pone.0037941 |
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