Small molecule-mediated inhibition of the oxidoreductase ERO1A restrains aggressive breast cancer by impairing VEGF and PD-L1 in the tumor microenvironment.

ABSTRACT: Cancer cells adapt to harsh environmental conditions by inducing the Unfolded Protein Response (UPR), of which ERO1A is a mediator. ERO1A aids protein folding by acting as a protein disulfide oxidase, and under cancer-related hypoxia conditions, it favors the folding of angiogenic VEGFA, leading tumor cells to thrive and spread. The upregulation of ERO1A in cancer cells, oppositely to the dispensability of ERO1A activity in healthy cells, renders ERO1A a perfect target for cancer therapy. Here, we report the upregulation of ERO1A in a cohort of aggressive triple-negative breast cancer (TNBC) patients in which ERO1A levels correlate with a higher risk of breast tumor recurrence and metastatic spread. For ERO1A target validation and therapy in TNBC, we designed new ERO1A inhibitors in a stru

SUBMITTER: Varone E 

PROVIDER: S-EPMC11833095 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature