Cancer is regarded as one of the world's most serious health issues. Glucose regulated protein (GRP78) exhibits a vital role in proliferation, invasion, and metastasis numerous cancer cells. Based on that, this study screened 390 natural compounds targeting GRP78 catalytic site. Among them, corynanthin, toyocamycin, nanaomycin were found to strongly bind with possess binding affinities -8.4, -8...

The glucose regulated protein 78 (GRP78) is a major chaperone of the endoplasmic reticulum, and a prosurvival component of the unfolded protein response. GRP78 is upregulated in many types of cancers, including breast cancer. Research has suggested that GRP78 overexpression confers chemoresistance to anti-estrogen agents through a mechanism involving the inhibition of a pro-apoptotic BH3-only p...

Acquired resistance is a common phenomenon for HCC patients who undergone sorafenib treatment, however the mechanism by which acquired resistance develops remains elusive. In this study, we found that GRP78 could be detected in the serum samples of HCC patients and the conditional medium of multiple HCC cell lines, suggesting that GRP78 is secreted by HCC cells. Further studies showed that secr...

GRP78 (glucose-regulated protein of 78 kDa) is traditionally regarded as a major ER (endoplasmic reticulum) chaperone facilitating protein folding and assembly, protein quality control, Ca(2+) binding and regulating ER stress signalling. It is a potent anti-apoptotic protein and plays a critical role in tumour cell survival, tumour progression and angiogenesis, metastasis and resistance to ther...

In human rabdomiosarcoma cells (TE671/RD) chronic exposure to 500 nM thapsigargin (a powerful inhibitor of the endoplasmic reticulum Ca2+-ATPases) resulted in the induction of the stress protein GRP78/BIP. Making use of the surface biotinylation method, followed by the isolation of the GRP78 using ATP-agarose affinity chromatography, it was found that a fraction of the thapsigargin-induced GRP7...

Introduction Bronchial epithelial cell death and airway inflammation induced by cigarette smoke (CS) have been involved in the pathogenesis of COPD. GRP78, belonging to heat shock protein 70 family, has been implicated in cell death and inflammation, while little is known about its roles in COPD. Here, we demonstrate that GRP78 regulates CS-induced necroptosis and injury in bronchial epithelial...

The recent discovery that GRP78/BiP, a typical endoplasmic reticulum (ER) lumenal chaperone, can be expressed on the cell surface, interacting with an increasing repertoire of surface proteins and acting as receptor in signaling pathways, represents a paradigm shift in its biological function. However, the mechanism of GRP78 trafficking from the ER to the cell surface is not well understood. Us...

Hypoxia renders tumor cells with reduced sensitivity and increased resistance to chemotherapeutic agents. One of the possible mechanisms underlying this unfavorable status is activation of the unfolded protein response (UPR) under hypoxic conditions, due to the upregulation of glucose-regulated protein 78 (GRP78) expression. GRP78, an endoplasmic reticulum chaperone protein and a key regulator ...

BACKGROUND Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine constitutively expressed by urothelial cells. During inflammatory stimuli, MIF is released into the lumen complexed to other proteins and these complexes can bind to urothelial cell-surface receptors to activate signaling pathways. Since MIF is complexed to alpha1-inhibitor III (A1-I3; a member of the alpha2-...

Despite the clinical benefit of the proteasome inhibitor bortezomib, multiple myeloma (MM) patients invariably relapse through poorly defined mechanisms. Myeloma cells inevitably develop chemoresistance that leads to disease relapse and patient-related deaths. Studies in tumor cell lines and biopsies obtained from patients refractory to therapy have revealed that myeloma cells adapt to stress b...