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The eEF2 kinase confers tumor cell adaptation to nutrient deprivation

The eEF2 kinase confers tumor cell adaptation to nutrient deprivation
The eEF2 kinase confers tumor cell adaptation to nutrient deprivation
Metabolic adaptation is essential for cell survival during nutrient deprivation. We report that eukaryotic elongation factor 2 kinase (eEF2K), which is activated by AMP-kinase (AMPK), confers cell survival under acute nutrient depletion by blocking translation elongation. Tumor cells exploit this pathway to adapt to nutrient deprivation by reactivating the AMPK-eEF2K axis. Adaptation of transformed cells to nutrient withdrawal is severely compromised in cells lacking eEF2K. Moreover, eEF2K knockdown restored sensitivity to acute nutrient deprivation in highly resistant human tumor cell lines. In vivo, overexpression of eEF2K rendered murine tumors remarkably resistant to caloric restriction. Expression of eEF2K strongly correlated with overall survival in human medulloblastoma and glioblastoma multiforme. Finally, C. elegans strains deficient in efk-1, the eEF2K ortholog, were severely compromised in their response to nutrient depletion. Our data highlight a conserved role for eEF2K in protecting cells from nutrient deprivation and in conferring tumor cell adaptation to metabolic stress.
0092-8674
1064-1079
Leprivier, G.
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Remke, M.
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Dubuc, A.
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Rotblat, B.
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Kool, M.
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Agnihotri, S.
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El-Naggar, A.
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Yu, B.
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Mateo, A.
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Somasekharan, S.
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Tognon, C.E.
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Mathers, J.
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Thomas, R.
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Barokas, A.
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Bowden, M.
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Smith, S.
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Wu, X.
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Korshunov, A.
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Hielscher, T.
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Northcott, P.A.
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McCabe, M.G.
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Delattre, O.
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Gleave, M.E.
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Jan, E.
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Proud, C.G.
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Pfister, S.M.
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Derry, B.
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Taylor, M.D.
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Sorensen, P.H.B.
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Leprivier, G.
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Remke, M.
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Dubuc, A.
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Rotblat, B.
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Kool, M.
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Agnihotri, S.
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El-Naggar, A.
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Yu, B.
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Mateo, A.
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Somasekharan, S.
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Tognon, C.E.
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Mathers, J.
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Thomas, R.
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Barokas, A.
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Bowden, M.
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Smith, S.
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Wu, X.
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Korshunov, A.
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Hielscher, T.
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Northcott, P.A.
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McCabe, M.G.
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Delattre, O.
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Gleave, M.E.
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Jan, E.
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Proud, C.G.
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Pfister, S.M.
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Derry, B.
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Taylor, M.D.
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Sorensen, P.H.B.
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Leprivier, G., Remke, M., Dubuc, A., Rotblat, B., Kool, M., Agnihotri, S., El-Naggar, A., Yu, B., Mateo, A., Somasekharan, S., Tognon, C.E., Mathers, J., Thomas, R., Barokas, A., Bowden, M., Smith, S., Wu, X., Korshunov, A., Hielscher, T., Northcott, P.A., McCabe, M.G., Delattre, O., Gleave, M.E., Jan, E., Proud, C.G., Pfister, S.M., Derry, B., Taylor, M.D. and Sorensen, P.H.B. (2013) The eEF2 kinase confers tumor cell adaptation to nutrient deprivation. Cell, 153 (5), 1064-1079. (doi:10.1016/j.cell.2013.04.055). (PMID:23706743)

Record type: Article

Abstract

Metabolic adaptation is essential for cell survival during nutrient deprivation. We report that eukaryotic elongation factor 2 kinase (eEF2K), which is activated by AMP-kinase (AMPK), confers cell survival under acute nutrient depletion by blocking translation elongation. Tumor cells exploit this pathway to adapt to nutrient deprivation by reactivating the AMPK-eEF2K axis. Adaptation of transformed cells to nutrient withdrawal is severely compromised in cells lacking eEF2K. Moreover, eEF2K knockdown restored sensitivity to acute nutrient deprivation in highly resistant human tumor cell lines. In vivo, overexpression of eEF2K rendered murine tumors remarkably resistant to caloric restriction. Expression of eEF2K strongly correlated with overall survival in human medulloblastoma and glioblastoma multiforme. Finally, C. elegans strains deficient in efk-1, the eEF2K ortholog, were severely compromised in their response to nutrient depletion. Our data highlight a conserved role for eEF2K in protecting cells from nutrient deprivation and in conferring tumor cell adaptation to metabolic stress.

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Published date: 23 May 2013
Organisations: Centre for Biological Sciences

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Local EPrints ID: 350254
URI: http://eprints.soton.ac.uk/id/eprint/350254
ISSN: 0092-8674
PURE UUID: 61ae9f4c-3e89-49cb-84d6-cadbd4b952a0

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Date deposited: 20 Mar 2013 13:02
Last modified: 14 Mar 2024 13:22

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Contributors

Author: G. Leprivier
Author: M. Remke
Author: A. Dubuc
Author: B. Rotblat
Author: M. Kool
Author: S. Agnihotri
Author: A. El-Naggar
Author: B. Yu
Author: A. Mateo
Author: S. Somasekharan
Author: C.E. Tognon
Author: J. Mathers
Author: R. Thomas
Author: A. Barokas
Author: M. Bowden
Author: S. Smith
Author: X. Wu
Author: A. Korshunov
Author: T. Hielscher
Author: P.A. Northcott
Author: M.G. McCabe
Author: O. Delattre
Author: M.E. Gleave
Author: E. Jan
Author: C.G. Proud
Author: S.M. Pfister
Author: B. Derry
Author: M.D. Taylor
Author: P.H.B. Sorensen

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