The Role of ERO1? in Modulating Cancer Progression and Immune Escape.
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ABSTRACT: Endoplasmic reticulum oxidoreductin-1 alpha (ERO1?) was originally shown to be an endoplasmic reticulum (ER) resident protein undergoing oxidative cycles in concert with protein disulfide isomerase (PDI) to promote proper protein folding and to maintain homeostasis within the ER. ERO1? belongs to the flavoprotein family containing a flavin adenine dinucleotide utilized in transferring of electrons during oxidation-reduction cycles. This family is used to maintain redox potentials and protein homeostasis within the ER. ERO1?'s location and function has since been shown to exist beyond the ER. Originally thought to exist solely in the ER, it has since been found to exist in the golgi apparatus, as well as in exosomes purified from patient samples. Besides aiding in protein folding of transmembrane and secretory proteins in conjunction with PDI, ERO1? is also known for formation of de novo disulfide bridges. Public databases, such as the Cancer Genome Atlas (TCGA) and The Protein Atlas, reveal ERO1? as a poor prognostic marker in multiple disease settings. Recent evidence indicates that ERO1? expression in tumor cells is a critical determinant of metastasis. However, the impact of increased ERO1? expression in tumor cells extends into the tumor microenvironment. Secretory proteins requiring ERO1? expression for proper folding have been implicated as being involved in immune escape through promotion of upregulation of programmed death ligand-1 (PD-L1) and stimulation of polymorphonuclear myeloid derived suppressor cells (PMN-MDSC's) via secretion of granulocytic colony stimulating factor (G-CSF). Hereby, ERO1? plays a pivotal role in cancer progression and potentially immune escape; making ERO1? an emerging attractive putative target for the treatment of cancer.
SUBMITTER: Johnson BD
PROVIDER: S-EPMC7894644 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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