eEF2K as a novel metastatic and prognostic biomarker in gastric cancer patients

Jiang, Mingxia; Ling, Qi; Jin, Kyong-Suk; Li, Lisha; Wu, Yiming; Song, Dongfeng; Gan, Junqing; Huang, Mei; Li, Yanjing; Song, Chengxin

doi:10.1016/j.prp.2021.153568

Cited by 10 publications

(7 citation statements)

References 42 publications

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“…Endothelial cells change dynamically during angiogenesis and this process is regulated by several genes [24]. More and more studies have shown that eEF2K is highly expressed in various tumor tissues and cells, and promotes tumor progression [25]. Our results indicated that eEF2K knockdown synergized STS to inhibit the angiogenesis of LUAD via TG2/IL-6/VEGFR2 pathway.…”

Section: Discussionmentioning

confidence: 61%

eEF2K knockdown synergizes STS to inhibit the angiogenesis of lung adenocarcinoma via TG2/IL-6/VEGFR2 pathway

Wang

Zou

et al. 2022

Preprint

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Background: Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Eukaryotic elongation factor 2 kinase (eEF2K) is considered to be a carcinogen, and Sulfotanshinone IIA sodium (STS) has been proved to have anticancer effect. However, their role in LUAD and its underlying mechanism remains unclear.Objective: To figuring out the roles of eEF2K and STS in angiogenesis of LUAD and their underlying mechanism.Methods: The mRNA levels of genes were detected by qRT-PCR. The levels of proteins were measured by Western blot. The secretion of IL-6 was assessed by ELISA. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by EdU assay and tubule formation assay, respectively.Results: Our results illustrated that eEF2K knockdown-LUAD cells synergize STS inhibited the proliferation and angiogenesis of HUVECs, eEF2K knockdown synergized STS inhibited the secretion of interleukin 6 (IL-6) in LUAD cells, and eEF2K knockdown-LUAD cells synergized STS to inhibit the proliferation and angiogenesis of HUVECs, which were dependent on IL-6 secretion and Transglutaminase 2 (TG2). Moreover, eEF2K knockdown-LUAD cells synergized STS inhibited IL-6/STAT3/VEGFR2 pathway depended on TG2. Conclusion: Our research ultimately illustrated that eEF2K knockdown synergized STS to inhibit the angiogenesis of LUAD via TG2/IL-6/VEGFR2 pathway.

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Section: Discussionmentioning

confidence: 61%

eEF2K knockdown synergizes STS to inhibit the angiogenesis of lung adenocarcinoma via TG2/IL-6/VEGFR2 pathway

Wang

Zou

et al. 2022

Preprint

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“…EEF2K can positively help to improve breast cancer cells' survival ability under nutrient deprivation or insufficient growth factor [45]. EEF2K is also a clinical indicator of metastasis and prognosis of stomach adenocarcinoma and could serve as a potential therapeutic target [46]. In our study, this PRG prognostic signature's association with EC progression can be preferably illustrated through the results of correlation analysis and stratified analysis, and this finding exerts satisfactory predicting power in terms of the survival period of EC patients.…”

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

A Novel Defined Pyroptosis-Related Gene Signature for Predicting the Prognosis of Endometrial Cancer

Liu

Zeng

et al. 2022

Disease Markers

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Endometrial carcinoma (EC) is the second major female genital malignancy. Genetic signatures may be an improved choice to predict the prognosis of EC patients. The relationship between pyroptosis and tumours has attracted much attention in recent years. Here, we constructed a new pyroptosis-related gene (PRG) signature for predicting the prognosis of EC. In this study, gene data and clinical information of EC patients were obtained from The Cancer Genome Atlas (TCGA). Following the identification of PRGs correlated with EC prognosis, we further investigate the bioinformatics functions of these PRGs by univariate Cox regression analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Then, we used the least absolute contraction and selection operator (LASSO) regression and multiple Cox regression analysis to construct a new PRG signature that contains seven PRGs (NFKB1, EEF2K, CTSV, MDM2, GZMB, PANX1, and PTEN) and performed the Kaplan-Meier (K-M) analysis, receiver operating characteristic curve (ROC) analysis, and principal component analysis (PCA) to evaluate the prognostic value of our novel PRG signature. Finally, we assessed the correlations between pyroptosis and immune cells/checkpoints through the CIBERSORT tool and single-sample gene set enrichment analysis (ssGSEA). The result suggested that our signature was powerful in predicting EC prognosis and may play a part in assessing response to immunotherapy in EC patients. In conclusion, our study established a novel PRG signature for EC, which can be used as an effective prognostic marker in clinical practice in the future.

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“…EE2FK is overexpressed in many metastatic cancer types and has been associated with poor prognosis [17,34]. A recent study highlighted the importance of eEF2K as a metastatic as well as prognostic biomarker in people diagnosed with gastric cancer [35]. A similar study done by Xie et al showed that si-RNA-mediated eEF2K silencing in human lung cancer cells suppressed the tumor growth and metastasis [36].…”

Section: Discussionmentioning

confidence: 99%

Impact of silencing eEF2K expression on the malignant properties of chordoma

et al. 2023

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Background Eukaryotic elongation factor 2 kinase (eukaryotic elongation factor 2 kinase, eEF2K) is a calcium calmodulin dependent protein kinase that keeps the highest energy consuming cellular process of protein synthesis under check through negative regulation. EEF2K pauses global protein synthesis rates at the translational elongation step by phosphorylating its only kown substrate elongation factor 2 (eEF2), a unique translocase activity in ekaryotic cells enabling the polypeptide chain elongation. Therefore, eEF2K is thought to preserve cellular energy pools particularly upon acute development of cellular stress conditions such as nutrient deprivation, hypoxia, or infections. Recently, high expression of this enzyme has been associated with poor prognosis in an array of solid tumor types. Therefore, in a growing number of studies tremendous effort is being directed to the development of treatment methods aiming to suppress eEF2K as a novel therapeutic approach in the ght against cancer.Methods In our study, we aimed to investigate the changes in the tumorigenicity of chordoma cells in presence of gene silencing for eEF2K. Taking a transient gene silencing approach using siRNA particles, eEF2K gene expression was suppressed in chordoma cells.ResultsSilencing eEF2K expression was associated with a slight increase in cellular proliferation and a decrease in death rates. Furthermore, no alteration in the sensitivity of chordoma cells to chemotherapy was detected in response to the decrease in eEF2K expression which intriguingly promoted suppression of cell migratory and invasion related properties. ConclusionOur ndings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.

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eEF2K as a novel metastatic and prognostic biomarker in gastric cancer patients

Cited by 10 publications

References 42 publications

eEF2K knockdown synergizes STS to inhibit the angiogenesis of lung adenocarcinoma via TG2/IL-6/VEGFR2 pathway

eEF2K knockdown synergizes STS to inhibit the angiogenesis of lung adenocarcinoma via TG2/IL-6/VEGFR2 pathway

A Novel Defined Pyroptosis-Related Gene Signature for Predicting the Prognosis of Endometrial Cancer

Impact of silencing eEF2K expression on the malignant properties of chordoma

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