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Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer

The inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that heme-oxygenase (HO-1) had a strong anti-tumoral effect in PCa. We previously undertook an in-depth proteomics study to build the HO-1 interactome in PCa. In this work, we used a bioin...

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Autores principales: Ortiz, Emiliano, Sanchis, Pablo, Bizzotto, Juan, Lage-Vickers, Sofia, Labanca, Estefania, Navone, Nora, Cotignola, Javier, Vazquez, Elba, Gueron, Geraldine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407234/
https://www.ncbi.nlm.nih.gov/pubmed/32640729
http://dx.doi.org/10.3390/biom10071005
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author Ortiz, Emiliano
Sanchis, Pablo
Bizzotto, Juan
Lage-Vickers, Sofia
Labanca, Estefania
Navone, Nora
Cotignola, Javier
Vazquez, Elba
Gueron, Geraldine
author_facet Ortiz, Emiliano
Sanchis, Pablo
Bizzotto, Juan
Lage-Vickers, Sofia
Labanca, Estefania
Navone, Nora
Cotignola, Javier
Vazquez, Elba
Gueron, Geraldine
author_sort Ortiz, Emiliano
collection PubMed
description The inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that heme-oxygenase (HO-1) had a strong anti-tumoral effect in PCa. We previously undertook an in-depth proteomics study to build the HO-1 interactome in PCa. In this work, we used a bioinformatics approach to address the biological significance of HO-1 interactors. Open-access PCa datasets were mined to address the clinical significance of the HO-1 interactome in human samples. HO-1 interactors were clustered into groups according to their expression profile in PCa patients. We focused on the myxovirus resistance gene (MX1) as: (1) it was significantly upregulated under HO-1 induction; (2) it was the most consistently downregulated gene in PCa vs. normal prostate; (3) its loss was associated with decreased relapse-free survival in PCa; and (4) there was a significant positive correlation between MX1 and HMOX1 in PCa patients. Further, MX1 was upregulated in response to endoplasmic reticulum stress (ERS), and this stress triggered apoptosis and autophagy in PCa cells. Strikingly, MX1 silencing reversed ERS. Altogether, we showcase MX1 as a novel HO-1 interactor and downstream target, associated with ERS in PCa and having a high impact in the clinical setting.
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spelling pubmed-74072342020-08-11 Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer Ortiz, Emiliano Sanchis, Pablo Bizzotto, Juan Lage-Vickers, Sofia Labanca, Estefania Navone, Nora Cotignola, Javier Vazquez, Elba Gueron, Geraldine Biomolecules Article The inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that heme-oxygenase (HO-1) had a strong anti-tumoral effect in PCa. We previously undertook an in-depth proteomics study to build the HO-1 interactome in PCa. In this work, we used a bioinformatics approach to address the biological significance of HO-1 interactors. Open-access PCa datasets were mined to address the clinical significance of the HO-1 interactome in human samples. HO-1 interactors were clustered into groups according to their expression profile in PCa patients. We focused on the myxovirus resistance gene (MX1) as: (1) it was significantly upregulated under HO-1 induction; (2) it was the most consistently downregulated gene in PCa vs. normal prostate; (3) its loss was associated with decreased relapse-free survival in PCa; and (4) there was a significant positive correlation between MX1 and HMOX1 in PCa patients. Further, MX1 was upregulated in response to endoplasmic reticulum stress (ERS), and this stress triggered apoptosis and autophagy in PCa cells. Strikingly, MX1 silencing reversed ERS. Altogether, we showcase MX1 as a novel HO-1 interactor and downstream target, associated with ERS in PCa and having a high impact in the clinical setting. MDPI 2020-07-06 /pmc/articles/PMC7407234/ /pubmed/32640729 http://dx.doi.org/10.3390/biom10071005 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ortiz, Emiliano
Sanchis, Pablo
Bizzotto, Juan
Lage-Vickers, Sofia
Labanca, Estefania
Navone, Nora
Cotignola, Javier
Vazquez, Elba
Gueron, Geraldine
Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer
title Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer
title_full Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer
title_fullStr Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer
title_full_unstemmed Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer
title_short Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer
title_sort myxovirus resistance protein 1 (mx1), a novel ho-1 interactor, tilts the balance of endoplasmic reticulum stress towards pro-death events in prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407234/
https://www.ncbi.nlm.nih.gov/pubmed/32640729
http://dx.doi.org/10.3390/biom10071005
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