» Articles » PMID: 21278783

Expression of Elongation Factor-2 Kinase Contributes to Anoikis Resistance and Invasion of Human Glioma Cells

Overview
Specialty Pharmacology
Date 2011 Feb 1
PMID 21278783
Citations 11
Authors
Affiliations
Soon will be listed here.
Abstract

Aim: To determine whether elongation factor-2 kinase (eEF-2 kinase) contributes to the malignant phenotype of glioblastoma multiforme by promoting the migration and invasion of glioma cells. The mechanism involved was also explored.

Methods: Human glioma cell lines T98G and LN-229 were used. The expression of eEF-2 kinase was silenced using siRNA, and the invasive potential of tumor cells was assessed using a wound-healing assay and a Matrigel invasion assay. Apoptosis was determined using propidium iodide (PI) staining and Western blot analysis of cleaved caspase-3.

Results: Silencing the expression of eEF-2 kinase by siRNA significantly suppressed both the migration and invasion of human glioma cells. Silencing eEF-2 kinase expression also sensitized glioma cells to anoikis, thereby decreasing tumor cell viability in the absence of attachment. Treatment of tumor cells with the caspase inhibitor z-VAD-fmk down-regulated Bim accumulation and abolished glioma cell sensitivity to anoikis.

Conclusion: The results suggest that the expression of eEF-2 kinase contributes to migration and invasion of human glioma cells by protecting them from anoikis. eEF-2 kinase expression may serve as a prognostic marker and a novel target for cancer therapy.

Citing Articles

Forms of Non-Apoptotic Cell Death and Their Role in Gliomas-Presentation of the Current State of Knowledge.

Nafe R, Hattingen E Biomedicines. 2024; 12(7).

PMID: 39062119 PMC: 11274595. DOI: 10.3390/biomedicines12071546.


Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings.

Begagic E, Pugonja R, Beculic H, celikovic A, Tandir Lihic L, Kadic Vukas S Brain Sci. 2023; 13(11).

PMID: 38002561 PMC: 10669565. DOI: 10.3390/brainsci13111602.


Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.

Gao X, Qian J, Zhang Y, Wang H, Cui J, Yang Y Proteome Sci. 2023; 21(1):14.

PMID: 37740172 PMC: 10517517. DOI: 10.1186/s12953-023-00216-7.


Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.

Muzyka L, Goff N, Choudhary N, Koltz M Int J Mol Sci. 2023; 24(13).

PMID: 37445633 PMC: 10341773. DOI: 10.3390/ijms241310456.


Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.

Zhu Z, Fang C, Xu H, Yuan L, Du Y, Ni Y Front Oncol. 2022; 12:976557.

PMID: 36046036 PMC: 9423707. DOI: 10.3389/fonc.2022.976557.


References
1.
Xu C, Chang C . Expression profiles of the genes associated with metabolism and transport of amino acids and their derivatives in rat liver regeneration. Amino Acids. 2007; 34(1):91-102. DOI: 10.1007/s00726-007-0576-2. View

2.
Zinck R, Cahill M, Kracht M, Sachsenmaier C, Hipskind R, Nordheim A . Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1. Mol Cell Biol. 1995; 15(9):4930-8. PMC: 230739. DOI: 10.1128/MCB.15.9.4930. View

3.
Collins N, Reginato M, Paulus J, Sgroi D, LaBaer J, Brugge J . G1/S cell cycle arrest provides anoikis resistance through Erk-mediated Bim suppression. Mol Cell Biol. 2005; 25(12):5282-91. PMC: 1140593. DOI: 10.1128/MCB.25.12.5282-5291.2005. View

4.
Salhia B, Tran N, Symons M, Winkles J, Rutka J, Berens M . Molecular pathways triggering glioma cell invasion. Expert Rev Mol Diagn. 2006; 6(4):613-26. DOI: 10.1586/14737159.6.4.613. View

5.
Arora S, Yang J, Hait W . Identification of the ubiquitin-proteasome pathway in the regulation of the stability of eukaryotic elongation factor-2 kinase. Cancer Res. 2005; 65(9):3806-10. DOI: 10.1158/0008-5472.CAN-04-4036. View