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Identification of breast cancer cell subtypes sensitive to ATG4B inhibition
Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding pat...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341851/ https://www.ncbi.nlm.nih.gov/pubmed/27556700 http://dx.doi.org/10.18632/oncotarget.11408 |
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author | Bortnik, Svetlana Choutka, Courtney Horlings, Hugo M. Leung, Samuel Baker, Jennifer H. Lebovitz, Chandra Dragowska, Wieslawa H. Go, Nancy E. Bally, Marcel B. Minchinton, Andrew I. Gelmon, Karen A. Gorski, Sharon M. |
author_facet | Bortnik, Svetlana Choutka, Courtney Horlings, Hugo M. Leung, Samuel Baker, Jennifer H. Lebovitz, Chandra Dragowska, Wieslawa H. Go, Nancy E. Bally, Marcel B. Minchinton, Andrew I. Gelmon, Karen A. Gorski, Sharon M. |
author_sort | Bortnik, Svetlana |
collection | PubMed |
description | Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target. In this study, we investigated the expression of ATG4B in breast cancer, a heterogeneous disease comprised of several molecular subtypes. We examined a panel of breast cancer cell lines, xenograft tumors, and breast cancer patient specimens for the protein expression of ATG4B, and found a positive association between HER2 and ATG4B protein expression. We showed that HER2-positive cells, but not HER2-negative breast cancer cells, require ATG4B to survive under stress. In HER2-positive cells, cytoprotective autophagy was dependent on ATG4B under both starvation and HER2 inhibition conditions. Combined knockdown of ATG4B and HER2 by siRNA resulted in a significant decrease in cell viability, and the combination of ATG4B knockdown with trastuzumab resulted in a greater reduction in cell viability compared to trastuzumab treatment alone, in both trastuzumab-sensitive and -resistant HER2 overexpressing breast cancer cells. Together these results demonstrate a novel association of ATG4B positive expression with HER2 positive breast cancers and indicate that this subtype is suitable for emerging ATG4B inhibition strategies. |
format | Online Article Text |
id | pubmed-5341851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53418512017-03-23 Identification of breast cancer cell subtypes sensitive to ATG4B inhibition Bortnik, Svetlana Choutka, Courtney Horlings, Hugo M. Leung, Samuel Baker, Jennifer H. Lebovitz, Chandra Dragowska, Wieslawa H. Go, Nancy E. Bally, Marcel B. Minchinton, Andrew I. Gelmon, Karen A. Gorski, Sharon M. Oncotarget Research Paper Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target. In this study, we investigated the expression of ATG4B in breast cancer, a heterogeneous disease comprised of several molecular subtypes. We examined a panel of breast cancer cell lines, xenograft tumors, and breast cancer patient specimens for the protein expression of ATG4B, and found a positive association between HER2 and ATG4B protein expression. We showed that HER2-positive cells, but not HER2-negative breast cancer cells, require ATG4B to survive under stress. In HER2-positive cells, cytoprotective autophagy was dependent on ATG4B under both starvation and HER2 inhibition conditions. Combined knockdown of ATG4B and HER2 by siRNA resulted in a significant decrease in cell viability, and the combination of ATG4B knockdown with trastuzumab resulted in a greater reduction in cell viability compared to trastuzumab treatment alone, in both trastuzumab-sensitive and -resistant HER2 overexpressing breast cancer cells. Together these results demonstrate a novel association of ATG4B positive expression with HER2 positive breast cancers and indicate that this subtype is suitable for emerging ATG4B inhibition strategies. Impact Journals LLC 2016-08-19 /pmc/articles/PMC5341851/ /pubmed/27556700 http://dx.doi.org/10.18632/oncotarget.11408 Text en Copyright: © 2016 Bortnik 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Bortnik, Svetlana Choutka, Courtney Horlings, Hugo M. Leung, Samuel Baker, Jennifer H. Lebovitz, Chandra Dragowska, Wieslawa H. Go, Nancy E. Bally, Marcel B. Minchinton, Andrew I. Gelmon, Karen A. Gorski, Sharon M. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition |
title | Identification of breast cancer cell subtypes sensitive to ATG4B inhibition |
title_full | Identification of breast cancer cell subtypes sensitive to ATG4B inhibition |
title_fullStr | Identification of breast cancer cell subtypes sensitive to ATG4B inhibition |
title_full_unstemmed | Identification of breast cancer cell subtypes sensitive to ATG4B inhibition |
title_short | Identification of breast cancer cell subtypes sensitive to ATG4B inhibition |
title_sort | identification of breast cancer cell subtypes sensitive to atg4b inhibition |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341851/ https://www.ncbi.nlm.nih.gov/pubmed/27556700 http://dx.doi.org/10.18632/oncotarget.11408 |
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