Inhibition of the FAD containing ER oxidoreductin 1 (Ero1) protein by EN-460 as a strategy for treatment of multiple myeloma.

ABSTRACT: Multiple myeloma (MM) cells demonstrate high basal endoplasmic reticulum (ER) stress and are typically exquisitely sensitive to agents such as proteasome inhibitors that activate the unfolded protein response. The flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum oxidoreductin enzyme (Ero1L) catalyzes de-novo disulfide bridge formation of ER resident proteins and contributes to proper protein folding. Here we show that increased Ero1L expression is prognostic of poor outcomes for MM patients relapsing on therapy. We propose that targeting protein folding via inhibition of Ero1L may represent a novel therapeutic strategy for the treatment of MM. In this report we show that treatment of MM cells with EN-460, a known inhibitor of ERO1L, was sufficient to inhibit cell prolif

SUBMITTER: Hayes KE 

PROVIDER: S-EPMC6554731 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature