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C/EBPβ LIP augments cell death by inducing osteoglycin

Many types of tumor cell are devoid of the extracellular matrix proteoglycan osteoglycin (Ogn), but its role in tumor biology is poorly studied. Here we show that RNAi of Ogn attenuates stress-triggered cell death, whereas its overexpression increases cell death. We found that the transcription fact...

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Autores principales: Wassermann-Dozorets, Rina, Rubinstein, Menachem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603828/
https://www.ncbi.nlm.nih.gov/pubmed/28383550
http://dx.doi.org/10.1038/cddis.2017.155
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author Wassermann-Dozorets, Rina
Rubinstein, Menachem
author_facet Wassermann-Dozorets, Rina
Rubinstein, Menachem
author_sort Wassermann-Dozorets, Rina
collection PubMed
description Many types of tumor cell are devoid of the extracellular matrix proteoglycan osteoglycin (Ogn), but its role in tumor biology is poorly studied. Here we show that RNAi of Ogn attenuates stress-triggered cell death, whereas its overexpression increases cell death. We found that the transcription factor C/EBPβ regulates the expression of Ogn. C/EBPβ is expressed as a full-length, active form (LAP) and as a truncated, dominant-negative form (LIP), and the LIP/LAP ratio is positively correlated with the extent of cell death under stress. For example, we reported that drug-resistant tumor cells lack LIP altogether, and its supplementation abolished their resistance to chemotherapy and to endoplasmic reticulum (ER) stress. Here we further show that elevated LIP/LAP ratio robustly increased Ogn expression and cell death under stress by modulating the mitogen-activated protein kinase/activator protein 1 pathway (MAPK/AP-1). Our findings suggest that LIP deficiency renders tumor cell resistant to ER stress by preventing the induction of Ogn.
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spelling pubmed-56038282017-09-22 C/EBPβ LIP augments cell death by inducing osteoglycin Wassermann-Dozorets, Rina Rubinstein, Menachem Cell Death Dis Original Article Many types of tumor cell are devoid of the extracellular matrix proteoglycan osteoglycin (Ogn), but its role in tumor biology is poorly studied. Here we show that RNAi of Ogn attenuates stress-triggered cell death, whereas its overexpression increases cell death. We found that the transcription factor C/EBPβ regulates the expression of Ogn. C/EBPβ is expressed as a full-length, active form (LAP) and as a truncated, dominant-negative form (LIP), and the LIP/LAP ratio is positively correlated with the extent of cell death under stress. For example, we reported that drug-resistant tumor cells lack LIP altogether, and its supplementation abolished their resistance to chemotherapy and to endoplasmic reticulum (ER) stress. Here we further show that elevated LIP/LAP ratio robustly increased Ogn expression and cell death under stress by modulating the mitogen-activated protein kinase/activator protein 1 pathway (MAPK/AP-1). Our findings suggest that LIP deficiency renders tumor cell resistant to ER stress by preventing the induction of Ogn. Nature Publishing Group 2017-04 2017-04-06 /pmc/articles/PMC5603828/ /pubmed/28383550 http://dx.doi.org/10.1038/cddis.2017.155 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Wassermann-Dozorets, Rina
Rubinstein, Menachem
C/EBPβ LIP augments cell death by inducing osteoglycin
title C/EBPβ LIP augments cell death by inducing osteoglycin
title_full C/EBPβ LIP augments cell death by inducing osteoglycin
title_fullStr C/EBPβ LIP augments cell death by inducing osteoglycin
title_full_unstemmed C/EBPβ LIP augments cell death by inducing osteoglycin
title_short C/EBPβ LIP augments cell death by inducing osteoglycin
title_sort c/ebpβ lip augments cell death by inducing osteoglycin
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603828/
https://www.ncbi.nlm.nih.gov/pubmed/28383550
http://dx.doi.org/10.1038/cddis.2017.155
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