Cell surface glucose-regulated protein 78 (GRP78) is upregulated in plasma cells of patients with multiple myeloma compared to monoclonal gammopathy of uncertain significance

Abstract

Multiple myeloma (MM) is characterised by paraprotein (PP) and/or serum free light chain (SFLC) production, a hypoxic tumour microenvironment (TME) and increased cellular stress. Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum stress-inducible molecular chaperone, is upregulated at times of cellular stress and acts to limit proteotoxicity and promote cell survival. Translocation of GRP78 to the cell surface (csGRP78) and interaction with cell signalling and survival pathways is emerging as a critical step providing tumour cells with a survival advantage.