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ADAR1-mediated regulation of melanoma invasion

Melanoma cells use different migratory strategies to exit the primary tumor mass and invade surrounding and subsequently distant tissues. We reported previously that ADAR1 expression is downregulated in metastatic melanoma, thereby facilitating proliferation. Here we show that ADAR1 silencing enhanc...

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Autores principales: Nemlich, Yael, Baruch, Erez Nissim, Besser, Michal Judith, Shoshan, Einav, Bar-Eli, Menashe, Anafi, Liat, Barshack, Iris, Schachter, Jacob, Ortenberg, Rona, Markel, Gal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981216/
https://www.ncbi.nlm.nih.gov/pubmed/29855470
http://dx.doi.org/10.1038/s41467-018-04600-2
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author Nemlich, Yael
Baruch, Erez Nissim
Besser, Michal Judith
Shoshan, Einav
Bar-Eli, Menashe
Anafi, Liat
Barshack, Iris
Schachter, Jacob
Ortenberg, Rona
Markel, Gal
author_facet Nemlich, Yael
Baruch, Erez Nissim
Besser, Michal Judith
Shoshan, Einav
Bar-Eli, Menashe
Anafi, Liat
Barshack, Iris
Schachter, Jacob
Ortenberg, Rona
Markel, Gal
author_sort Nemlich, Yael
collection PubMed
description Melanoma cells use different migratory strategies to exit the primary tumor mass and invade surrounding and subsequently distant tissues. We reported previously that ADAR1 expression is downregulated in metastatic melanoma, thereby facilitating proliferation. Here we show that ADAR1 silencing enhances melanoma cell invasiveness and ITGB3 expression. The enhanced invasion is reversed when ITGB3 is blocked with antibodies. Re-expression of wild-type or catalytically inactive ADAR1 establishes this mechanism as independent of RNA editing. We demonstrate that ADAR1 controls ITGB3 expression both at the post-transcriptional and transcriptional levels, via miR-22 and PAX6 transcription factor, respectively. These are proven here as direct regulators of ITGB3 expression. miR-22 expression is controlled by ADAR1 via FOXD1 transcription factor. Clinical relevance is demonstrated in patient-paired progression tissue microarray using immunohistochemistry. The novel ADAR1-dependent and RNA-editing-independent regulation of invasion, mediated by ITGB3, strongly points to a central involvement of ADAR1 in cancer progression and metastasis.
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spelling pubmed-59812162018-06-04 ADAR1-mediated regulation of melanoma invasion Nemlich, Yael Baruch, Erez Nissim Besser, Michal Judith Shoshan, Einav Bar-Eli, Menashe Anafi, Liat Barshack, Iris Schachter, Jacob Ortenberg, Rona Markel, Gal Nat Commun Article Melanoma cells use different migratory strategies to exit the primary tumor mass and invade surrounding and subsequently distant tissues. We reported previously that ADAR1 expression is downregulated in metastatic melanoma, thereby facilitating proliferation. Here we show that ADAR1 silencing enhances melanoma cell invasiveness and ITGB3 expression. The enhanced invasion is reversed when ITGB3 is blocked with antibodies. Re-expression of wild-type or catalytically inactive ADAR1 establishes this mechanism as independent of RNA editing. We demonstrate that ADAR1 controls ITGB3 expression both at the post-transcriptional and transcriptional levels, via miR-22 and PAX6 transcription factor, respectively. These are proven here as direct regulators of ITGB3 expression. miR-22 expression is controlled by ADAR1 via FOXD1 transcription factor. Clinical relevance is demonstrated in patient-paired progression tissue microarray using immunohistochemistry. The novel ADAR1-dependent and RNA-editing-independent regulation of invasion, mediated by ITGB3, strongly points to a central involvement of ADAR1 in cancer progression and metastasis. Nature Publishing Group UK 2018-05-31 /pmc/articles/PMC5981216/ /pubmed/29855470 http://dx.doi.org/10.1038/s41467-018-04600-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nemlich, Yael
Baruch, Erez Nissim
Besser, Michal Judith
Shoshan, Einav
Bar-Eli, Menashe
Anafi, Liat
Barshack, Iris
Schachter, Jacob
Ortenberg, Rona
Markel, Gal
ADAR1-mediated regulation of melanoma invasion
title ADAR1-mediated regulation of melanoma invasion
title_full ADAR1-mediated regulation of melanoma invasion
title_fullStr ADAR1-mediated regulation of melanoma invasion
title_full_unstemmed ADAR1-mediated regulation of melanoma invasion
title_short ADAR1-mediated regulation of melanoma invasion
title_sort adar1-mediated regulation of melanoma invasion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981216/
https://www.ncbi.nlm.nih.gov/pubmed/29855470
http://dx.doi.org/10.1038/s41467-018-04600-2
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