info:eu-repo/semantics/article
Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer
Fecha
2020-07Registro en:
Ortiz, Emiliano Germán; Sanchis, Pablo Antonio; Bizzotto, Juan Antonio; Lage Vickers, Sofia; Labanca, Estefania; et al.; Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer; Molecular Diversity Preservation International; Biomolecules; 10; 7; 7-2020; 1-23
2218-273X
CONICET Digital
CONICET
Autor
Ortiz, Emiliano Germán
Sanchis, Pablo Antonio
Bizzotto, Juan Antonio
Lage Vickers, Sofia
Labanca, Estefania
Navone, Nora
Cotignola, Javier Hernan
Vazquez, Elba Susana
Gueron, Geraldine
Resumen
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.