RGD Reference Report - Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC. - Rat Genome Database

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Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC.

Authors: Pott, Leona L  Hagemann, Sascha  Reis, Henning  Lorenz, Kristina  Bracht, Thilo  Herold, Thomas  Skryabin, Boris V  Megger, Dominik A  Kälsch, Julia  Weber, Frank  Sitek, Barbara  Baba, Hideo A 
Citation: Pott LL, etal., Oncotarget. 2017 Feb 14;8(7):11950-11962. doi: 10.18632/oncotarget.14447.
RGD ID: 153298915
Pubmed: PMID:28060762   (View Abstract at PubMed)
PMCID: PMC5355317   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.14447   (Journal Full-text)

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells.
CONCLUSION: eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma exacerbatesHEP 153298915protein:increased expression and increased phosphorylation:liver (human)RGD 

Objects Annotated

Genes (Homo sapiens)
EEF2  (eukaryotic translation elongation factor 2)


Additional Information