@article{8c0dfc1b79734c748df92f6c55edeff9,
title = "XThe eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation",
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. PaperClip",
author = "Gabriel Leprivier and Marc Remke and Barak Rotblat and Adrian Dubuc and Mateo, {Abigail Rachele F.} and Marcel Kool and Sameer Agnihotri and Amal El-Naggar and Bin Yu and {Prakash Somasekharan}, Syam and Brandon Faubert and Ga{\"e}lle Bridon and Tognon, {Cristina E.} and Joan Mathers and Ryan Thomas and Amy Li and Adi Barokas and Brian Kwok and Mary Bowden and Stephanie Smith and Xiaochong Wu and Andrey Korshunov and Thomas Hielscher and Northcott, {Paul A.} and Galpin, {Jason D.} and Ahern, {Christopher A.} and Ye Wang and McCabe, {Martin G.} and Collins, {V. Peter} and Jones, {Russell G.} and Michael Pollak and Olivier Delattre and Gleave, {Martin E.} and Eric Jan and Pfister, {Stefan M.} and Proud, {Christopher G.} and Derry, {W. Brent} and Taylor, {Michael D.} and Sorensen, {Poul H.}",
note = "Funding Information: We thank T. Tang, M. Robertson, and C. Chow for technical assistance and B. Fonseca (McGill University), S. Aparicio, S. Mullaly, T. Ng (UBC), J.A. Pospisilik, and R. Teperino (Max Planck Institute, Freiburg) for helpful discussions. This work was supported by the Canadian Cancer Society Research Institute and the British Columbia Cancer Foundation (to P.H.S.) through generous donations from Team Finn and other riders in the Ride to Conquer Cancer and by the National Institutes of Health (CA159859), the Terry Fox Research Institute, and the Pediatric Brain Tumor Foundation (to M.D.T.).",
year = "2013",
month = may,
day = "23",
doi = "10.1016/j.cell.2013.04.055",
language = "American English",
volume = "153",
pages = "1064",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "5",
}
