Impact of silencing eEF2K expression on the malignant properties of chordoma
(2023) In Molecular Biology Reports 50(4). p.3011-3022- Abstract
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... (More)
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 fight 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. Results: Silencing 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. Conclusion: Our findings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.
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- author
- Aydemir, Esra ; Tüysüz, Emre Can LU ; Bayrak, Ömer Faruk ; Tecimel, Didem ; Hızlı-Deniz, Ayşen Aslı and Şahin, Fikrettin
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Chordoma, eEF2K, Migration, siRNAs
- in
- Molecular Biology Reports
- volume
- 50
- issue
- 4
- pages
- 3011 - 3022
- publisher
- Springer
- external identifiers
-
- scopus:85146394609
- pmid:36652154
- ISSN
- 0301-4851
- DOI
- 10.1007/s11033-023-08257-z
- language
- English
- LU publication?
- yes
- id
- fd0fbd85-c16d-4eb6-b14d-4197143f94ef
- date added to LUP
- 2023-02-20 08:37:46
- date last changed
- 2024-06-13 14:18:05
@article{fd0fbd85-c16d-4eb6-b14d-4197143f94ef,
abstract = {{<p>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 fight 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. Results: Silencing 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. Conclusion: Our findings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.</p>}},
author = {{Aydemir, Esra and Tüysüz, Emre Can and Bayrak, Ömer Faruk and Tecimel, Didem and Hızlı-Deniz, Ayşen Aslı and Şahin, Fikrettin}},
issn = {{0301-4851}},
keywords = {{Chordoma; eEF2K; Migration; siRNAs}},
language = {{eng}},
number = {{4}},
pages = {{3011--3022}},
publisher = {{Springer}},
series = {{Molecular Biology Reports}},
title = {{Impact of silencing eEF2K expression on the malignant properties of chordoma}},
url = {{http://dx.doi.org/10.1007/s11033-023-08257-z}},
doi = {{10.1007/s11033-023-08257-z}},
volume = {{50}},
year = {{2023}},
}