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Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis
TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis by engaging its death receptors (DRs) 4 and/or 5 on targeted cells. Clinical attempts to stimulate this apoptotic pathway for cancer therapy, including the use of recombinant human TRAIL (rhTRAIL) or receptor agonistic antibodies, have...
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/PMC5955420/ https://www.ncbi.nlm.nih.gov/pubmed/29796187 http://dx.doi.org/10.18632/oncotarget.25297 |
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author | Bozza, William P. Zhang, Yaqin Zhang, Baolin |
author_facet | Bozza, William P. Zhang, Yaqin Zhang, Baolin |
author_sort | Bozza, William P. |
collection | PubMed |
description | TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis by engaging its death receptors (DRs) 4 and/or 5 on targeted cells. Clinical attempts to stimulate this apoptotic pathway for cancer therapy, including the use of recombinant human TRAIL (rhTRAIL) or receptor agonistic antibodies, have been underway for over a decade. Unfortunately, these agents have only shown limited therapeutic effects due largely to tumor resistance arising from mechanisms yet to be defined. Here we show that intermediate filament proteins, keratin 8 and keratin 18 (K8/K18), negatively regulate TRAIL induced apoptosis. K8/K18 protein levels are consistently higher in TRAIL-resistant cells compared to TRAIL-sensitive cells in a panel of breast cancer cell lines. Blockade of K8 increased expression of DR5 on the surface of targeted cells and sensitized the cells to TRAIL-induced apoptosis. Conversely, ectopic expression of K8/K18 downregulated DR5 protein expression. K8/K18 appears to negatively regulate apoptosis signaling via DR5 in breast cancer cells. Our findings warrant additional studies to determine if K8/K18 could be a predictor of tumor resistance to DR5-targeted therapies. |
format | Online Article Text |
id | pubmed-5955420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59554202018-05-24 Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis Bozza, William P. Zhang, Yaqin Zhang, Baolin Oncotarget Research Paper TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis by engaging its death receptors (DRs) 4 and/or 5 on targeted cells. Clinical attempts to stimulate this apoptotic pathway for cancer therapy, including the use of recombinant human TRAIL (rhTRAIL) or receptor agonistic antibodies, have been underway for over a decade. Unfortunately, these agents have only shown limited therapeutic effects due largely to tumor resistance arising from mechanisms yet to be defined. Here we show that intermediate filament proteins, keratin 8 and keratin 18 (K8/K18), negatively regulate TRAIL induced apoptosis. K8/K18 protein levels are consistently higher in TRAIL-resistant cells compared to TRAIL-sensitive cells in a panel of breast cancer cell lines. Blockade of K8 increased expression of DR5 on the surface of targeted cells and sensitized the cells to TRAIL-induced apoptosis. Conversely, ectopic expression of K8/K18 downregulated DR5 protein expression. K8/K18 appears to negatively regulate apoptosis signaling via DR5 in breast cancer cells. Our findings warrant additional studies to determine if K8/K18 could be a predictor of tumor resistance to DR5-targeted therapies. Impact Journals LLC 2018-05-01 /pmc/articles/PMC5955420/ /pubmed/29796187 http://dx.doi.org/10.18632/oncotarget.25297 Text en Copyright: © 2018 Bozza 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 (http://creativecommons.org/licenses/by/3.0/) 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 Bozza, William P. Zhang, Yaqin Zhang, Baolin Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis |
title | Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis |
title_full | Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis |
title_fullStr | Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis |
title_full_unstemmed | Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis |
title_short | Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis |
title_sort | cytokeratin 8/18 protects breast cancer cell lines from trail-induced apoptosis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955420/ https://www.ncbi.nlm.nih.gov/pubmed/29796187 http://dx.doi.org/10.18632/oncotarget.25297 |
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