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Autophagy processes are dependent on EGF receptor signaling
Autophagy is a not well-understood conserved mechanism activated during nutritional deprivation in order to maintain cellular homeostasis. In the present study, we investigated the correlations between autophagy, apoptosis and the MAPK pathways in melanoma cell lines. We demonstrated that during sta...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084397/ https://www.ncbi.nlm.nih.gov/pubmed/30100990 http://dx.doi.org/10.18632/oncotarget.25708 |
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author | De Iuliis, Vincenzo Marino, Antonio Caruso, Marika Capodifoglio, Sabrina Flati, Vincenzo Marynuk, Anna Marricareda, Valeria Ursi, Sebastiano Lanuti, Paola Talora, Claudio Conti, Pio Martinotti, Stefano Toniato, Elena |
author_facet | De Iuliis, Vincenzo Marino, Antonio Caruso, Marika Capodifoglio, Sabrina Flati, Vincenzo Marynuk, Anna Marricareda, Valeria Ursi, Sebastiano Lanuti, Paola Talora, Claudio Conti, Pio Martinotti, Stefano Toniato, Elena |
author_sort | De Iuliis, Vincenzo |
collection | PubMed |
description | Autophagy is a not well-understood conserved mechanism activated during nutritional deprivation in order to maintain cellular homeostasis. In the present study, we investigated the correlations between autophagy, apoptosis and the MAPK pathways in melanoma cell lines. We demonstrated that during starvation the EGF receptor mediated signaling activates many proteins involved in the MAPK pathway. Our data also suggest a previously unidentified link between the EGFR and Beclin-1 in melanoma cell line. We demonstrated that, following starvation, EGFR binds and tyrosine-phosphorylates Beclin-1, suggesting that it may play a key inhibitory role in the early stage of starvation, possibly through the Beclin-1 sequestration. Furthermore, EGFR releases Beclin-1 and allows initiating steps of the autophagic process. Interestingly enough, when the EGFR pathway was blocked by anti-EGF antibodies, immunoprecipitated Beclin-1 did not bind the phospho-EGFR. In addition, an extended binding of p-Bcl2 either with Beclin-1 or with Bax was observed with a decreased activation of the stress-induced JNK kinase, thus avoiding the transduction pathways that activate autophagy and apoptosis, respectively. For this reason, we advance the hypothesis that the activation of the EGFR is a necessary event that allows the ignition and progression of the autophagic process, at least in melanoma cells. |
format | Online Article Text |
id | pubmed-6084397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-60843972018-08-10 Autophagy processes are dependent on EGF receptor signaling De Iuliis, Vincenzo Marino, Antonio Caruso, Marika Capodifoglio, Sabrina Flati, Vincenzo Marynuk, Anna Marricareda, Valeria Ursi, Sebastiano Lanuti, Paola Talora, Claudio Conti, Pio Martinotti, Stefano Toniato, Elena Oncotarget Research Paper Autophagy is a not well-understood conserved mechanism activated during nutritional deprivation in order to maintain cellular homeostasis. In the present study, we investigated the correlations between autophagy, apoptosis and the MAPK pathways in melanoma cell lines. We demonstrated that during starvation the EGF receptor mediated signaling activates many proteins involved in the MAPK pathway. Our data also suggest a previously unidentified link between the EGFR and Beclin-1 in melanoma cell line. We demonstrated that, following starvation, EGFR binds and tyrosine-phosphorylates Beclin-1, suggesting that it may play a key inhibitory role in the early stage of starvation, possibly through the Beclin-1 sequestration. Furthermore, EGFR releases Beclin-1 and allows initiating steps of the autophagic process. Interestingly enough, when the EGFR pathway was blocked by anti-EGF antibodies, immunoprecipitated Beclin-1 did not bind the phospho-EGFR. In addition, an extended binding of p-Bcl2 either with Beclin-1 or with Bax was observed with a decreased activation of the stress-induced JNK kinase, thus avoiding the transduction pathways that activate autophagy and apoptosis, respectively. For this reason, we advance the hypothesis that the activation of the EGFR is a necessary event that allows the ignition and progression of the autophagic process, at least in melanoma cells. Impact Journals LLC 2018-07-13 /pmc/articles/PMC6084397/ /pubmed/30100990 http://dx.doi.org/10.18632/oncotarget.25708 Text en Copyright: © 2018 De Iuliis et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper De Iuliis, Vincenzo Marino, Antonio Caruso, Marika Capodifoglio, Sabrina Flati, Vincenzo Marynuk, Anna Marricareda, Valeria Ursi, Sebastiano Lanuti, Paola Talora, Claudio Conti, Pio Martinotti, Stefano Toniato, Elena Autophagy processes are dependent on EGF receptor signaling |
title | Autophagy processes are dependent on EGF receptor signaling |
title_full | Autophagy processes are dependent on EGF receptor signaling |
title_fullStr | Autophagy processes are dependent on EGF receptor signaling |
title_full_unstemmed | Autophagy processes are dependent on EGF receptor signaling |
title_short | Autophagy processes are dependent on EGF receptor signaling |
title_sort | autophagy processes are dependent on egf receptor signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084397/ https://www.ncbi.nlm.nih.gov/pubmed/30100990 http://dx.doi.org/10.18632/oncotarget.25708 |
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