Glucose-regulated protein 78 (GRP78) is a stress protein and molecular chaperone. It usually is located in the endoplasmic reticulum and can be translocated to the cell surface as a receptor for a variety of ligands. GRP78 is implicated in a series of biological processes, such as protein folding and assembly, angiogenesis, metastasis, and regulation of endoplasmic reticulum stress signaling. However, the molecular mechanism of GRP78 remains unclear. Recently, the article by Rondas et al. (1) demonstrated that inflammatory stress, induced by the cytokines interleukin-1β and interferon-γ, lead to citrullination of GRP78 in β-cells and there were autoantibodies and effector T cells against citrullinated GRP78 in prediabetic NOD mice, which indicated that GRP78 might play an important role in the progress of diseases.
Other studies have reported the similar results. The article by Lu et al. (2) manifested that anti-citrullinated protein antibodies activated nuclear factor-κB and tumor necrosis factor-α through binding to citrullinated GRP78 via activated extracellular signal–related kinase 1/2 and Jun NH2-terminal kinase in rheumatic arthritis. The article by Bon et al. (3) indicated that GRP78 autoimmune responses in smokers were associated with emphysema and osteoporosis. Furthermore, the article by Wang et al. (4) suggested that GRP78 was the drug target of isoliquiritigenin to enhance breast cancer stem cell chemosensitivity. In addition, the article by Yuan et al. (5) demonstrated that GRP78 promoted invasion of pancreatic cancer through activation of focal adhesion kinase and Jun NH2-terminal kinase.
Taken together, these findings suggest that GRP78 might play an important role in the progress of diabetes, rheumatic arthritis, emphysema, osteoporosis, and breast cancer stem cell chemosensitivity. We read with interest the article by Rondas et al. (1) and thought that GRP78 might be a good promising drug target for diseases.
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Funding. This work was supported by the school fund project of Anhui Medical University (grant no. 2015xkj031) and the doctoral research fund project of the Second Affiliated Hospital of Anhui Medical University (grant no. 2014bkj034).
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
