title: The 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:
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Research Centre, University of British Columbia (UBC), Vancouver, BC V5Z1L4, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Leprivier
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.forename: Barak
authors.initials: B
authors.lastname: Rotblat
authors.forename: Adrian
authors.initials: A
authors.lastname: Dubuc
authors.forename: Abigail-Rachele F
authors.initials: AR
authors.lastname: Mateo
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.forename: Sameer
authors.initials: S
authors.lastname: Agnihotri
authors.forename: Amal
authors.initials: A
authors.lastname: El-Naggar
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Syam Prakash
authors.initials: SP
authors.lastname: Somasekharan
authors.forename: Brandon
authors.initials: B
authors.lastname: Faubert
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bridon
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Tognon
authors.forename: Joan
authors.initials: J
authors.lastname: Mathers
authors.forename: Ryan
authors.initials: R
authors.lastname: Thomas
authors.forename: Amy
authors.initials: A
authors.lastname: Li
authors.forename: Adi
authors.initials: A
authors.lastname: Barokas
authors.forename: Brian
authors.initials: B
authors.lastname: Kwok
authors.forename: Mary
authors.initials: M
authors.lastname: Bowden
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith
authors.forename: Xiaochong
authors.initials: X
authors.lastname: Wu
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.forename: Paul A
authors.initials: PA
authors.lastname: Northcott
authors.forename: Jason D
authors.initials: JD
authors.lastname: Galpin
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ahern
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Martin G
authors.initials: MG
authors.lastname: McCabe
authors.forename: V Peter
authors.initials: VP
authors.lastname: Collins
authors.forename: Russell G
authors.initials: RG
authors.lastname: Jones
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.forename: Eric
authors.initials: E
authors.lastname: Jan
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Proud
authors.forename: W Brent
authors.initials: WB
authors.lastname: Derry
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Poul H
authors.initials: PH
authors.lastname: Sorensen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000503:physiopathology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D054736:Elongation Factor 2 Kinase / Q000235:genetics / Q000378:metabolism*; D005508:Food Deprivation; D005909:Glioblastoma / Q000503:physiopathology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000503:physiopathology*; D010441:Peptide Chain Elongation, Translational; D020652:Peptide Elongation Factor 2 / Q000378:metabolism; D015398:Signal Transduction; D014183:Transplantation, Heterologous
chemical_list: D020652:Peptide Elongation Factor 2; D054736:Elongation Factor 2 Kinase; D055372:AMP-Activated Protein Kinases