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Loss of Ambra1 promotes melanoma growth and invasion
Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100102/ https://www.ncbi.nlm.nih.gov/pubmed/33953176 http://dx.doi.org/10.1038/s41467-021-22772-2 |
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author | Di Leo, Luca Bodemeyer, Valérie Bosisio, Francesca M. Claps, Giuseppina Carretta, Marco Rizza, Salvatore Faienza, Fiorella Frias, Alex Khan, Shawez Bordi, Matteo Pacheco, Maria P. Di Martino, Julie Bravo-Cordero, Jose J. Daniel, Colin J. Sears, Rosalie C. Donia, Marco Madsen, Daniel H. Guldberg, Per Filomeni, Giuseppe Sauter, Thomas Robert, Caroline De Zio, Daniela Cecconi, Francesco |
author_facet | Di Leo, Luca Bodemeyer, Valérie Bosisio, Francesca M. Claps, Giuseppina Carretta, Marco Rizza, Salvatore Faienza, Fiorella Frias, Alex Khan, Shawez Bordi, Matteo Pacheco, Maria P. Di Martino, Julie Bravo-Cordero, Jose J. Daniel, Colin J. Sears, Rosalie C. Donia, Marco Madsen, Daniel H. Guldberg, Per Filomeni, Giuseppe Sauter, Thomas Robert, Caroline De Zio, Daniela Cecconi, Francesco |
author_sort | Di Leo, Luca |
collection | PubMed |
description | Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecule in Beclin-1-Regulated Autophagy (Ambra1) contributes to melanoma development. Indeed, we show that Ambra1 deficiency confers accelerated tumor growth and decreased overall survival in Braf/Pten-mutated mouse models of melanoma. Also, we demonstrate that Ambra1 deletion promotes melanoma aggressiveness and metastasis by increasing cell motility/invasion and activating an EMT-like process. Moreover, we show that Ambra1 deficiency in melanoma impacts extracellular matrix remodeling and induces hyperactivation of the focal adhesion kinase 1 (FAK1) signaling, whose inhibition is able to reduce cell invasion and melanoma growth. Overall, our findings identify a function for AMBRA1 as tumor suppressor in melanoma, proposing FAK1 inhibition as a therapeutic strategy for AMBRA1 low-expressing melanoma. |
format | Online Article Text |
id | pubmed-8100102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81001022021-05-11 Loss of Ambra1 promotes melanoma growth and invasion Di Leo, Luca Bodemeyer, Valérie Bosisio, Francesca M. Claps, Giuseppina Carretta, Marco Rizza, Salvatore Faienza, Fiorella Frias, Alex Khan, Shawez Bordi, Matteo Pacheco, Maria P. Di Martino, Julie Bravo-Cordero, Jose J. Daniel, Colin J. Sears, Rosalie C. Donia, Marco Madsen, Daniel H. Guldberg, Per Filomeni, Giuseppe Sauter, Thomas Robert, Caroline De Zio, Daniela Cecconi, Francesco Nat Commun Article Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecule in Beclin-1-Regulated Autophagy (Ambra1) contributes to melanoma development. Indeed, we show that Ambra1 deficiency confers accelerated tumor growth and decreased overall survival in Braf/Pten-mutated mouse models of melanoma. Also, we demonstrate that Ambra1 deletion promotes melanoma aggressiveness and metastasis by increasing cell motility/invasion and activating an EMT-like process. Moreover, we show that Ambra1 deficiency in melanoma impacts extracellular matrix remodeling and induces hyperactivation of the focal adhesion kinase 1 (FAK1) signaling, whose inhibition is able to reduce cell invasion and melanoma growth. Overall, our findings identify a function for AMBRA1 as tumor suppressor in melanoma, proposing FAK1 inhibition as a therapeutic strategy for AMBRA1 low-expressing melanoma. Nature Publishing Group UK 2021-05-05 /pmc/articles/PMC8100102/ /pubmed/33953176 http://dx.doi.org/10.1038/s41467-021-22772-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Di Leo, Luca Bodemeyer, Valérie Bosisio, Francesca M. Claps, Giuseppina Carretta, Marco Rizza, Salvatore Faienza, Fiorella Frias, Alex Khan, Shawez Bordi, Matteo Pacheco, Maria P. Di Martino, Julie Bravo-Cordero, Jose J. Daniel, Colin J. Sears, Rosalie C. Donia, Marco Madsen, Daniel H. Guldberg, Per Filomeni, Giuseppe Sauter, Thomas Robert, Caroline De Zio, Daniela Cecconi, Francesco Loss of Ambra1 promotes melanoma growth and invasion |
title | Loss of Ambra1 promotes melanoma growth and invasion |
title_full | Loss of Ambra1 promotes melanoma growth and invasion |
title_fullStr | Loss of Ambra1 promotes melanoma growth and invasion |
title_full_unstemmed | Loss of Ambra1 promotes melanoma growth and invasion |
title_short | Loss of Ambra1 promotes melanoma growth and invasion |
title_sort | loss of ambra1 promotes melanoma growth and invasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100102/ https://www.ncbi.nlm.nih.gov/pubmed/33953176 http://dx.doi.org/10.1038/s41467-021-22772-2 |
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