scholarly journals Isthmin is a novel vascular permeability inducer that functions through cell-surface GRP78-mediated Src activation

2015 ◽  
Vol 107 (1) ◽  
pp. 131-142 ◽  
Author(s):  
Shruthi Venugopal ◽  
Mo Chen ◽  
Wupeng Liao ◽  
Shi Yin Er ◽  
Wai-Shiu Fred Wong ◽  
...  
Keyword(s):  
Cell Surface ◽  
Vascular Permeability ◽  
Cell Surface Grp78 ◽  
Src Activation

Cell Surface GRP78

2018 ◽  
pp. 41-62 ◽  
Author(s):  
Yuan-Li Tsai ◽  
Amy S. Lee
Keyword(s):  
Cell Surface ◽  
Cell Surface Grp78

scholarly journals Neuropilin-1 and heparan sulfate proteoglycans cooperate in cellular uptake of nanoparticles functionalized by cationic cell-penetrating peptides

2015 ◽  
Vol 1 (10) ◽  
pp. e1500821 ◽  
Author(s):  
Hong-Bo Pang ◽  
Gary B. Braun ◽  
Erkki Ruoslahti
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Vascular Permeability ◽  
Mammalian Cells ◽  
Cell Penetrating Peptides ◽  
Proteolytic Processing ◽  
Cell Surface Receptor ◽  
Neuropilin 1 ◽  
Cell Penetrating ◽  
Surface Receptor

Cell-penetrating peptides (CPPs) have been widely used to deliver nanomaterials and other types of macromolecules into mammalian cells for therapeutic and diagnostic use. Cationic CPPs that bind to heparan sulfate (HS) proteoglycans on the cell surface induce potent endocytosis; however, the role of other surface receptors in this process is unclear. We describe the convergence of an HS-dependent pathway with the C-end rule (CendR) mechanism that enables peptide ligation with neuropilin-1 (NRP1), a cell surface receptor known to be involved in angiogenesis and vascular permeability. NRP1 binds peptides carrying a positive residue at the carboxyl terminus, a feature that is compatible with cationic CPPs, either intact or after proteolytic processing. We used CPP and CendR peptides, as well as HS- and NRP1-binding motifs from semaphorins, to explore the commonalities and differences of the HS and NRP1 pathways. We show that the CendR-NRP1 interaction determines the ability of CPPs to induce vascular permeability. We also show at the ultrastructural level, using a novel cell entry synchronization method, that both the HS and NRP1 pathways can initiate a macropinocytosis-like process and visualize these CPP-cargo complexes going through various endosomal compartments. Our results provide new insights into how CPPs exploit multiple surface receptor pathways for intracellular delivery.

Abstract 4202: Peptide probes binding to radiation-inducible cell surface GRP78 as a novel targeting strategy for various tumors

2016 ◽  
Author(s):  
Vaishali Kapoor ◽  
David Dadey ◽  
Kim Nguyen ◽  
Hua Li ◽  
Buck Rogers ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Surface Grp78 ◽  
Peptide Probes ◽  
Targeting Strategy

scholarly journals Targeting cell surface GRP78 enhances pancreatic cancer radiosensitivity through YAP/TAZ protein signaling

2019 ◽  
Vol 294 (38) ◽  
pp. 13939-13952 ◽  
Author(s):  
Udhayakumar Gopal ◽  
Yvonne Mowery ◽  
Kenneth Young ◽  
Salvatore Vincent Pizzo
Keyword(s):  
Pancreatic Cancer ◽  
Cell Surface ◽  
Protein Signaling ◽  
Cell Surface Grp78

Cell surface GRP78 activation by anti-GRP78 autoantibodies in relation to prostate tumour growth via tissue factor activation.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 31-31
Author(s):  
Ali Al-Hashimi ◽  
Richard Austin ◽  
Bobby Shayegan
Keyword(s):  
Mouse Model ◽  
Cell Surface ◽  
Tumor Growth ◽  
Tissue Factor ◽  
Scid Mouse ◽  
Cell Activation ◽  
Promote Cell Proliferation ◽  
Scid Mouse Model ◽  
Cell Surface Grp78 ◽  
The Unfolded Protein Response

31 Background: Prostate cancer (PC) is characterized by increased prothrombotic state due to enhanced tissue factor (TF) expression/procoagulant activity (PCA). We and others observed that GRP78, a molecular chaperone, is expressed on the surface of PC cells where it functions as a signaling receptor to promote cell proliferation and survival. Further, exposure of GRP78 on the surface of PC cells stimulates the production of anti-GRP78 autoantibodies in PC patients. We have reported that binding of these autoantibodies to cell surface GRP78 enhances TF PCA. We hypothesize that this autoantibody/cell surface GRP78 complex interaction increases PC progression and that disruption of this complex would represent a viable target for the treatment of advanced PC. Methods: Wild type, TF knockdown DU145 cells, and NOD/SCID mouse model system was used to investigate the effect of anti-GRP78 autoantibodies on tumor growth. Protein expression was determined using western blotting and qRT-PCR. TF activity was determined using the TF PCA continuous assay. Blood samples from patients diagnosed with PC were obtained from the Ontario Tumour Bank and St. Joseph’s Hamilton. Results: Pre-prostatectomy patients demonstrated high levels of anti-GRP78 autoantibodies (60-100µg/ml) vs. healthy individuals (5-10µg/ml). These titers were significantly reduced 24-weeks post prostatectomy. We show here that anti-GRP78 autoantibodies upregulate TF and its PCA through a mechanism involving depletion of ER Ca2+ stores. This very effect on ER Ca2+ stores also caused activation of the unfolded protein response, a pro-survival cellular pathway. Furthermore, these autoantibodies were shown to accelerate tumor growth in a NOD/SCID mouse model. Finally, heparin and low molecular weight heparin were shown to interfere with the binding of these antibodies to cancer cells and prevent PC cell activation. Conclusions: We have identified the function of an agent in patients' blood, anti-GRP78 autoantibodies, that correlate with PC stage in patients and increase TF PCA and promote PC progression in mice. The effect of this autoantibody can be reversed using heparin, thus, this acts as a new potential therapeutic target for PC.

scholarly journals Activation of cell surface GRP78 decreases endoplasmic reticulum stress and neuronal death

2017 ◽  
Vol 24 (9) ◽  
pp. 1518-1529 ◽  
Author(s):  
Morgane Louessard ◽  
Isabelle Bardou ◽  
Eloïse Lemarchand ◽  
Audrey M Thiebaut ◽  
Jérôme Parcq ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Surface ◽  
Neuronal Death ◽  
Cell Surface Grp78

Cell-surface GRP78 facilitates colorectal cancer cell migration and invasion

2013 ◽  
Vol 45 (5) ◽  
pp. 987-994 ◽  
Author(s):  
Zongwei Li ◽  
Lichao Zhang ◽  
Yarui Zhao ◽  
Hanqing Li ◽  
Hong Xiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cell Surface ◽  
Cancer Cell ◽  
Colorectal Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion ◽  
Cell Surface Grp78

scholarly journals The role of c-Src in the invasion and metastasis of hepatocellular carcinoma cells induced by association of cell surface GRP78 with activated α2M

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Song Zhao ◽  
Hongdan Li ◽  
Qingjun Wang ◽  
Chang Su ◽  
Guan Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Surface ◽  
Carcinoma Cells ◽  
Invasion And Metastasis ◽  
Hepatocellular Carcinoma Cells ◽  
Cell Surface Grp78

Binding of anti-GRP78 autoantibodies to cell surface GRP78 promotes cancer progression by activating tissue factor procoagulant activity

2012 ◽  
Vol 129 ◽  
pp. S158
Author(s):  
A.A. Al-Hashimi ◽  
F. Majeed ◽  
M. Gonzalez-Gronow ◽  
R.C. Austin
Keyword(s):  
Cell Surface ◽  
Tissue Factor ◽  
Cancer Progression ◽  
Procoagulant Activity ◽  
Cell Surface Grp78
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