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.
1064-1079
Leprivier, G.
75e88370-cc50-418f-956c-31d4306bc4a5
Remke, M.
7a9a61f5-7995-4004-b1e4-b413fca90b8d
Dubuc, A.
c746f249-8bc3-4c96-87d8-39602c6dfeae
Rotblat, B.
a41ba057-187b-4168-b3e4-8c22fec09eb2
Kool, M.
dbd949b7-2d57-4291-992b-2e1e69e56482
Agnihotri, S.
05339980-57c9-4c42-b8d2-cf5b27f07586
El-Naggar, A.
b79df455-af0c-4664-ae8a-9a34b3bc69b7
Yu, B.
37bf1660-c4b9-4a56-a86a-d7821eafb8b2
Mateo, A.
88c2a4a0-08c7-47da-8e71-49e4a438c090
Somasekharan, S.
b793c695-0368-4288-a6f5-5e92bde47855
Tognon, C.E.
ca12eb73-e408-4f37-851b-3e97a77d5d6b
Mathers, J.
690c2764-65b7-4792-b560-4b5dd7f7f279
Thomas, R.
6814ea6d-818e-4088-882f-2b87f0147d2a
Barokas, A.
b8155d0c-3e0d-4fc9-b5ff-c362eb6f02ca
Bowden, M.
79eb9365-e0c0-414c-b428-1805cff66d58
Smith, S.
8904521d-3b46-4112-8566-e08de3e011a5
Wu, X.
b6ec2d37-5357-42db-a350-a73969909549
Korshunov, A.
bc85c168-d246-46b6-ac97-63de84b57701
Hielscher, T.
26c08ced-254d-4ab4-81d2-192241d57b55
Northcott, P.A.
d0520faa-4b40-446d-ac8b-6d51fba242d0
McCabe, M.G.
e061ec29-f0e6-41cf-bb35-e93d09edc220
Delattre, O.
016dd3ed-9cc0-4220-a731-cea58efe75fb
Gleave, M.E.
17b2bd37-ebaf-4979-b1ed-1a81a896c630
Jan, E.
daf0179d-2d2d-48df-a14c-9a6ed300de51
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
Pfister, S.M.
f2eab0dc-4068-4b06-b24e-426cb3e51276
Derry, B.
d2964f72-dda3-4dbd-acfe-63ce0c891e10
Taylor, M.D.
891fa06e-f89f-4a98-97e3-812addf8b6c6
Sorensen, P.H.B.
09f46587-741b-47eb-8e4e-e6506ea623e4
23 May 2013
Leprivier, G.
75e88370-cc50-418f-956c-31d4306bc4a5
Remke, M.
7a9a61f5-7995-4004-b1e4-b413fca90b8d
Dubuc, A.
c746f249-8bc3-4c96-87d8-39602c6dfeae
Rotblat, B.
a41ba057-187b-4168-b3e4-8c22fec09eb2
Kool, M.
dbd949b7-2d57-4291-992b-2e1e69e56482
Agnihotri, S.
05339980-57c9-4c42-b8d2-cf5b27f07586
El-Naggar, A.
b79df455-af0c-4664-ae8a-9a34b3bc69b7
Yu, B.
37bf1660-c4b9-4a56-a86a-d7821eafb8b2
Mateo, A.
88c2a4a0-08c7-47da-8e71-49e4a438c090
Somasekharan, S.
b793c695-0368-4288-a6f5-5e92bde47855
Tognon, C.E.
ca12eb73-e408-4f37-851b-3e97a77d5d6b
Mathers, J.
690c2764-65b7-4792-b560-4b5dd7f7f279
Thomas, R.
6814ea6d-818e-4088-882f-2b87f0147d2a
Barokas, A.
b8155d0c-3e0d-4fc9-b5ff-c362eb6f02ca
Bowden, M.
79eb9365-e0c0-414c-b428-1805cff66d58
Smith, S.
8904521d-3b46-4112-8566-e08de3e011a5
Wu, X.
b6ec2d37-5357-42db-a350-a73969909549
Korshunov, A.
bc85c168-d246-46b6-ac97-63de84b57701
Hielscher, T.
26c08ced-254d-4ab4-81d2-192241d57b55
Northcott, P.A.
d0520faa-4b40-446d-ac8b-6d51fba242d0
McCabe, M.G.
e061ec29-f0e6-41cf-bb35-e93d09edc220
Delattre, O.
016dd3ed-9cc0-4220-a731-cea58efe75fb
Gleave, M.E.
17b2bd37-ebaf-4979-b1ed-1a81a896c630
Jan, E.
daf0179d-2d2d-48df-a14c-9a6ed300de51
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
Pfister, S.M.
f2eab0dc-4068-4b06-b24e-426cb3e51276
Derry, B.
d2964f72-dda3-4dbd-acfe-63ce0c891e10
Taylor, M.D.
891fa06e-f89f-4a98-97e3-812addf8b6c6
Sorensen, P.H.B.
09f46587-741b-47eb-8e4e-e6506ea623e4