Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Translational Research Centre in Oncohaematology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Translational Research Centre in Oncohaematology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Cancer Lett. 2022 Jan 1;524:1-14. doi: 10.1016/j.canlet.2021.10.004. Epub 2021 Oct 9.
Glucose-related protein 78 (GRP78) is a chaperone protein localized primarily in the endoplasmic reticulum (ER) lumen, where it helps in proper protein folding by targeting misfolded proteins and facilitating protein assembly. In stressed cells, GRP78 is translocated to the cell surface (csGRP78) where it binds to various ligands and triggers different intracellular pathways. Thus, csGRP78 expression is associated with cancer, involved in the maintenance and progression of the disease. Extracellular exposition of csGRP78 leads to the production of autoantibodies as observed in patients with prostate or ovarian cancer, in which the ability to target csGRP78 affects the tumor development. Present on the surface of cancer cells and not normal cells in vivo, csGRP78 represents an interesting target for therapeutic antibody strategies. Here we give an overview of the csGRP78 function in the cell and its role in oncogenesis, thereby providing insight into the clinical value of GRP78 monoclonal antibodies for cancer prognosis and treatment.
葡萄糖相关蛋白 78（GRP78）是一种主要定位于内质网（ER）腔中的伴侣蛋白，它通过靶向错误折叠的蛋白质并促进蛋白质组装，帮助正确折叠蛋白质。在应激细胞中，GRP78 易位到细胞膜表面（csGRP78），在那里它与各种配体结合并触发不同的细胞内途径。因此，csGRP78 的表达与癌症相关，参与疾病的维持和进展。csGRP78 的细胞外暴露导致自身抗体的产生，如前列腺癌或卵巢癌患者中观察到的那样，其中靶向 csGRP78 的能力影响肿瘤的发展。csGRP78 存在于癌细胞表面，而不存在于体内正常细胞中，因此是治疗性抗体策略的一个有趣靶点。在这里，我们概述了 csGRP78 在细胞中的功能及其在肿瘤发生中的作用，从而深入了解 GRP78 单克隆抗体在癌症预后和治疗中的临床价值。
