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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...

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Autores principales: Schmidt, Jennifer, Riechers, Alexander, Stoll, Raphael, Amann, Thomas, Fink, Florian, Spruss, Thilo, Gronwald, Wolfram, König, Burkhard, Hellerbrand, Claus, Bosserhoff, Anja Katrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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