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...

P-glycoprotein (P-gp) overexpression is associated with poor prognosis and drug-resistance in osteosarcoma (OS), but the underlying mechanisms remain incompletely understood. Here, we examined the regulation of P-gp, GRP78, and phospho-Akt in doxorubicin (DOX)-treated OS cells. DOX induced P-gp expression, which was associated with increased GRP78 levels and Akt activation in vitro and in vivo....

Heat shock protein 70 (HSP70) is frequently overexpressed in a variety of human malignancies and protects cancer cells against apoptosis in response to various stresses. The bioflavonoid quercetin inhibits HSP70 expression and induces cancer cells apoptosis. In the present study, we have investigated the effects of HSP70 down-regulation on the unfolded protein response (UPR) and addressed a nov...

Glucose-regulated protein 78 (GRP78) is a chaperone protein that has a high frequency in tumor cells. Normally it is found in the endoplasmic reticulum to assist in protein folding, but under cellular stress, GRP78 influences proliferative signaling pathways at the cell surface. The increased expression elicits autoantibody production, providing a biomarker of ovarian cancer, as well as other t...

Clusterin (CLU) is a stress-activated chaperone, which plays an important role in cancer development and progression through promoting cell survival. However, the exact mechanism of how CLU exerts its cell protective role under ER stress condition is still unclear. Therefore, in order to explore the molecular mechanisms by which CLU inhibited ER stress-induced apoptosis, HCC cell lines were tre...

GRP78 is a major endoplasmic reticulum chaperone as well as a master regulator of the unfolded protein response. In addition to playing an essential role in early embryonic development, recent studies have emerged specifically implicating GRP78 and chaperone integrity in the aging process and age-related diseases. Another exciting discovery is the regulation of GRP78 by insulin/IGF-1 signaling ...

Class A scavenger receptor (SR-A) plays an important role in macrophage adhesion. However, the underlying mechanism remains unclear. We previously found that 78 kDa glucose-regulated protein (GRP78) inhibited SR-A-mediated ligand internalization into macrophage by binding to SR-A. The aim of the study was to investigate whether GRP78 could regulate SR-A-mediated cell adhesion. We demonstrated t...

Glucose-regulated protein 78 (GRP78)/BiP is a multifunctional protein which plays a major role in endoplasmic reticulum (ER) protein processing, protein quality control, maintaining ER homeostasis, and controlling cell signaling and viability. Previously, using a transgene-induced mammary tumor model, we showed that Grp78 heterozygosity impeded cancer growth through suppression of tumor cell pr...