Reconstructed mung bean trypsin inhibitor targeting cell surface GRP78 induces apoptosis and inhibits tumor growth in colorectal cancer

Li, Zongwei; Zhao, Chao; Li, Zhuoyu; Zhao, Yarui; Shan, Shuhua; Shi, Tonglin; Li, Jianguo

doi:10.1016/j.biocel.2013.11.022

Cited by 35 publications

(19 citation statements)

References 15 publications

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“…3F). Consistent with the above results, GRP78 and SLC1A5 are positively correlated in human colon cancer xenograft tissue in SCID mice [23] (Fig. 3G).…”

Section: Resultssupporting

confidence: 86%

GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the β-catenin signaling

Wang

et al. 2014

Oncotarget

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To support the high rates of proliferation, cancer cells undergo the metabolic reprogramming: aerobic glycolysis and glutamine addiction. Though glucose regulated protein 78 (GRP78) is a glucose-sensing protein and frequently highly expressed in tumor cells, its roles in glucose and glutamine metabolic regulation remain poorly unknown. We report here that glucose deficiency-induced GRP78 enhances β-catenin signaling and consequently promotes its downstream c-Myc-mediated glutamine metabolism in colorectal cancer cells. Mechanistically, GRP78 elevates intracellular free β-catenin level via disruption of adenomatous polyposis coli (APC)-β-catenin and E-cadherin-β-catenin protein complexes. Notably, overexpression of GRP78 causes APC protein downregulation in proteasome- and lysosome-independent manners. Further mechanistic studies reveal that GRP78 facilitates the extracellular release of APC, thereby rendering the liberation of β-catenin from APC. Furthermore, GRP78 acts through both hindering E-cadherin expression and impairing the interaction of E-cadherin with β-catenin to indirectly and directly influence E-cadherin-β-catenin complex stability. Our study reveals that GRP78 is a novel molecular link between metabolic alterations and signal transduction during tumor progression.

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“…3F). Consistent with the above results, GRP78 and SLC1A5 are positively correlated in human colon cancer xenograft tissue in SCID mice [23] (Fig. 3G).…”

Section: Resultssupporting

confidence: 86%

GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the β-catenin signaling

Wang

et al. 2014

Oncotarget

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“…There are multiple mechanisms for the role of GRP78 in CRC cancer cells migration and invasion [28][29][30][31]. In the present study, the results showed weak correlation between GRP78 protein expression and CRC metastasis.…”

Section: Discussioncontrasting

confidence: 53%

Expression of glucose regulated protein 78 (GRP78) determines colorectal cancer response to chemotherapy

Mhaidat

Alzoubi

Almomani

et al. 2015

CBM

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“…The GRP78 binding peptides have been conjugated to nanoparticles or liposomes for more efficient drug delivery 145,149 , and such agents are able to home to endothelial cells in tumours, suppressing growth and prolonged survival of colon carcinoma bearing mice 82 . Furthermore, a reconstructed protein containing GRP78 binding peptide and mung bean trypsin inhibitor displays targeted anti-cancer effects both in vitro and in vivo in colorectal cancer 150 .…”

Section: Targeting Grpsmentioning

confidence: 99%

Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential

2014

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Preface The glucose regulated proteins (GRPs) are stress inducible chaperones majorly residing in the endoplasmic reticulum (ER) and the mitochondria. Recent advances reveal that the GRPs serve distinct functions from the related heat shock proteins (HSPs), and they can be actively translocated to other cellular locations and assume novel functions controlling signaling, proliferation, invasion, apoptosis, inflammation and immunity. Mouse models further identified their specific roles in development, tumorigenesis, metastasis and angiogenesis. This Review describes their discovery, regulation and their biological functions in cancer. Promising agents using or targeting the GRPs are being developed, and their efficacy as anti-cancer therapeutics is also discussed.

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Reconstructed mung bean trypsin inhibitor targeting cell surface GRP78 induces apoptosis and inhibits tumor growth in colorectal cancer

Cited by 35 publications

References 15 publications

GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the β-catenin signaling

GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the β-catenin signaling

Expression of glucose regulated protein 78 (GRP78) determines colorectal cancer response to chemotherapy

Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential

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