ArticleJournal of hepatology2015
Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis.
Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- DNAJB4/HLJ1 deficiency sensitizes diethylnitrosamine-induced hepatocarcinogenesis with peritumoral STAT3 activation.Cell biology and toxicology · 2024Article
- CK2α-mediated phosphorylation of GRP94 facilitates the metastatic cascade in triple-negative breast cancer.Cell death discovery · 2024Article
- Natural compound Alternol actives multiple endoplasmic reticulum stress-responding pathways contributing to cell death.Frontiers in pharmacology · 2024Article
- Prognosis and therapeutic significance of IGF-1R-related signaling pathway gene signature in glioma.Frontiers in cell and developmental biology · 2024Article
- Cellular gp96 upregulates AFP expression by blocking NR5A2 SUMOylation and ubiquitination in hepatocellular carcinoma.Journal of molecular cell biology · 2023Article
- Article
- Review
- In vitro culture at 39 °C during hepatic maturation of human ES cells facilitates hepatocyte-like cell functions.Scientific reports · 2022Article
- Extracellular Vesicle Signatures and Post-Translational Protein Deimination in Purple Sea Urchin (Biology · 2021Article
- Cell Surface GRP94 as a Novel Emerging Therapeutic Target for Monoclonal Antibody Cancer Therapy.Cells · 2021Review
- Transcriptional signatures of Zika virus infection in astrocytes.Journal of neurovirology · 2021Article
- Comprehensive analysis reveals GRP94 is associated with worse prognosis of breast cancer.Translational cancer research · 2021Article
- Molecular Chaperone GRP94/GP96 in Cancers: Oncogenesis and Therapeutic Target.Frontiers in oncology · 2021Review
- Molecular Stressors Engender Protein Connectivity Dysfunction through Aberrant N-Glycosylation of a Chaperone.Cell reports · 2020Article
- Overexpression of molecule GRP94 favors tumor progression in lung adenocarcinoma by interaction with regulatory T cells.Thoracic cancer · 2020Article
- Upregulation of Serum Sphingosine (d18:1)-1-P Potentially Contributes to Distinguish HCC Including AFP-Negative HCC From Cirrhosis.Frontiers in oncology · 2020Article
- GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells.Scientific reports · 2019Article
- Endoplasmic Reticulum Stress Causes Liver Cancer Cells to Release Exosomal miR-23a-3p and Up-regulate Programmed Death Ligand 1 Expression in Macrophages.Hepatology (Baltimore, Md.) · 2019Article
- Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function.International journal of molecular sciences · 2019Review
- Prognostic value of the mRNA expression of members of the HSP90 family in non-small cell lung cancer.Experimental and therapeutic medicine · 2019Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsgp96, or grp94, is an endoplasmic reticulum (ER)-localized heat shock protein 90 paralog that acts as a protein chaperone and plays an important role for example in ER homeostasis, ER stress, Wnt and integrin signaling, and calcium homeostasis, which are vital processes in oncogenesis. However, the cancer-intrinsic function of gp96 remains controversial.
methodsWe studied the roles of gp96 in liver biology in mice via an Albumin promoter-driven Cre recombinase-mediated disruption of gp96 gene, hsp90b1. The impact of gp96 status on hepatic carcinogenesis in response to diethyl-nitrosoamine (DENA) was probed. The roles of gp96 on human hepatocellular carcinoma cells (HCC) were also examined pharmacologically with a targeted gp96 inhibitor.
resultsWe demonstrated that gp96 maintains liver development and hepatocyte function in vivo, and its loss genetically promotes adaptive accumulation of long chain ceramides, accompanied by steatotic regeneration of residual gp96+ hepatocytes. The need for compensatory expansion of gp96+ cells in the gp96- background predisposes mice to develop carcinogen-induced hepatic hyperplasia and cancer from gp96+ but not gp96- hepatocytes. We also found that genetic and pharmacological inhibition of gp96 in human HCCs perturbed multiple growth signals, and attenuated proliferation and expansion.
conclusionsgp96 is a pro-oncogenic chaperone and an attractive therapeutic target for HCC.
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