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Beclin 1 regulates growth factor receptor signaling in breast cancer
Beclin 1 is a haplo-insufficient tumor suppressor that is decreased in many human tumors. The function of Beclin 1 in cancer has been attributed primarily to its role in the degradative process of macroautophagy. However, Beclin 1 is a core component of the Vps34/Class III PI3K (PI3KC3) and Vps15/p1...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522409/ https://www.ncbi.nlm.nih.gov/pubmed/25639875 http://dx.doi.org/10.1038/onc.2014.454 |
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author | Rohatgi, Rasika A. Janusis, Jenny Leonard, Deborah Bellvé, Karl D. Fogarty, Kevin E. Baehrecke, Eric H. Corvera, Silvia Shaw, Leslie M. |
author_facet | Rohatgi, Rasika A. Janusis, Jenny Leonard, Deborah Bellvé, Karl D. Fogarty, Kevin E. Baehrecke, Eric H. Corvera, Silvia Shaw, Leslie M. |
author_sort | Rohatgi, Rasika A. |
collection | PubMed |
description | Beclin 1 is a haplo-insufficient tumor suppressor that is decreased in many human tumors. The function of Beclin 1 in cancer has been attributed primarily to its role in the degradative process of macroautophagy. However, Beclin 1 is a core component of the Vps34/Class III PI3K (PI3KC3) and Vps15/p150 complex that regulates multiple membrane trafficking events. In the current study, we describe an alternative mechanism of action for Beclin 1 in breast cancer involving its control of growth factor receptor signaling. We identify a specific stage of early endosome maturation that is regulated by Beclin 1, the transition of APPL1-containing phosphatidyIinositol 3-phosphate-negative (PI3P(-)) endosomes to PI3P(+) endosomes. Beclin 1 regulates PI3P production in response to growth factor stimulation to control the residency time of growth factor receptors in the PI3P(-)/APPL(+) signaling competent compartment. As a result, suppression of BECN1 sustains growth factor stimulated AKT and ERK activation resulting in increased breast carcinoma cell invasion. In human breast tumors, Beclin 1 expression is inversely correlated with AKT and ERK phosphorylation. Our data identify a novel role for Beclin 1 in regulating growth factor signaling and reveal a mechanism by which loss of Beclin 1 expression would enhance breast cancer progression. |
format | Online Article Text |
id | pubmed-4522409 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-45224092016-04-16 Beclin 1 regulates growth factor receptor signaling in breast cancer Rohatgi, Rasika A. Janusis, Jenny Leonard, Deborah Bellvé, Karl D. Fogarty, Kevin E. Baehrecke, Eric H. Corvera, Silvia Shaw, Leslie M. Oncogene Article Beclin 1 is a haplo-insufficient tumor suppressor that is decreased in many human tumors. The function of Beclin 1 in cancer has been attributed primarily to its role in the degradative process of macroautophagy. However, Beclin 1 is a core component of the Vps34/Class III PI3K (PI3KC3) and Vps15/p150 complex that regulates multiple membrane trafficking events. In the current study, we describe an alternative mechanism of action for Beclin 1 in breast cancer involving its control of growth factor receptor signaling. We identify a specific stage of early endosome maturation that is regulated by Beclin 1, the transition of APPL1-containing phosphatidyIinositol 3-phosphate-negative (PI3P(-)) endosomes to PI3P(+) endosomes. Beclin 1 regulates PI3P production in response to growth factor stimulation to control the residency time of growth factor receptors in the PI3P(-)/APPL(+) signaling competent compartment. As a result, suppression of BECN1 sustains growth factor stimulated AKT and ERK activation resulting in increased breast carcinoma cell invasion. In human breast tumors, Beclin 1 expression is inversely correlated with AKT and ERK phosphorylation. Our data identify a novel role for Beclin 1 in regulating growth factor signaling and reveal a mechanism by which loss of Beclin 1 expression would enhance breast cancer progression. 2015-02-02 2015-10-16 /pmc/articles/PMC4522409/ /pubmed/25639875 http://dx.doi.org/10.1038/onc.2014.454 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Rohatgi, Rasika A. Janusis, Jenny Leonard, Deborah Bellvé, Karl D. Fogarty, Kevin E. Baehrecke, Eric H. Corvera, Silvia Shaw, Leslie M. Beclin 1 regulates growth factor receptor signaling in breast cancer |
title | Beclin 1 regulates growth factor receptor signaling in breast cancer |
title_full | Beclin 1 regulates growth factor receptor signaling in breast cancer |
title_fullStr | Beclin 1 regulates growth factor receptor signaling in breast cancer |
title_full_unstemmed | Beclin 1 regulates growth factor receptor signaling in breast cancer |
title_short | Beclin 1 regulates growth factor receptor signaling in breast cancer |
title_sort | beclin 1 regulates growth factor receptor signaling in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522409/ https://www.ncbi.nlm.nih.gov/pubmed/25639875 http://dx.doi.org/10.1038/onc.2014.454 |
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