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 G.; SANCHIS, PABLO A; BIZZOTO, JUAN; LAGE VICKERS, SOFIA; LABANCA, ESTEFANIA; NAVONE, NORA; COTIGNOLA, JAVIER; VAZQUEZ ELBA; GUERON, GERALDINE

Biomolecules

MDPI

Año: 2020

2218-273X

Background: The inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that 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. Methods: Open-access PCa datasets were mined to address the clinical significance of HO-1 interactome in human samples. Results: 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 up-regulated under HO-1 induction; 2) it was the most consistently down-regulated 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 up-regulated in response to endoplasmic reticulum stress (ERS) and this stress triggered apoptosis and autophagy in PCa cells. Strikingly, MX1 silencing reversed ERS. Conclusion: we showcase MX1 as a novel HO-1 interactor and downstream target, associated with ERS in PCa and with a high impact in the clinical setting.