Research Advances of ERO1 in Tumor Biology: Mechanisms and Therapeutic Target

内质网氧化还原酶1 (ERO1)家族是一类定位于内质网的黄素氧化还原酶，主要负责接受蛋白质内二硫键成键时所产生的电子，从而维持内质网中氧化还原稳态，在蛋白质氧化折叠、维持钙离子稳态等过程中发挥重要的作用。已有研究发现相较于正常组织，ERO1在多种肿瘤中的表达均发生明显上调，并通过调节内质网应激、细胞死亡和肿瘤微环境等机制，增强肿瘤细胞的应激抗性，促进肿瘤的恶性进展，因此，ERO1有可能成为抗肿瘤药物研发的重要靶点。本文将对近年来ERO1家族相关的结构功能，ERO1在肿瘤发展中的作用和靶向ERO1的抗肿瘤机制等方向的研究进行综述。The endoplasmic reticulum oxidoreductase 1 (ERO1) family represents a class of flavoprotein oxidoreductases localized primarily in the endoplasmic reticulum (ER). These enzymes function as critical electron acceptors during disulfide bond formation in protein folding, thereby maintaining ER redox homeostasis and playing essential roles in oxidative protein folding and calcium ion homeostasis regulation. Emerging studies have demonstrated significant upregulation of ERO1 expression across multiple tumor types compared to normal tissues. Mechanistically, ERO1 enhances tumor cell stress resistance and promotes malignant progression through modulation of ER stress responses, cell death, and tumor microenvironment. Consequently, ERO1 has emerged as a promising therapeutic target for inhibitor development. This article comprehensively reviews recent advances in the structural-functional characteristics of ERO1 family members, their multifaceted roles in tumor progression, and mechanistic insights into ERO1-targeted antitumor strategies.