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.
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Acknowledgements
This project was supported by the National Natural Sciences Foundation of China (K113416510) and Natural Science Foundation of Jiangsu Province of China (BK2010224) and US Public Health Service R01CA135038.
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Zhang, L., Zhang, Y., Liu, Xy. et al. Expression of elongation factor-2 kinase contributes to anoikis resistance and invasion of human glioma cells. Acta Pharmacol Sin 32, 361–367 (2011). https://doi.org/10.1038/aps.2010.213
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DOI: https://doi.org/10.1038/aps.2010.213
