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dc.contributor.authorSaavedra-García, P
dc.contributor.authorRoman-Trufero, M
dc.contributor.authorAl-Sadah, HA
dc.contributor.authorBlighe, K
dc.contributor.authorLópez-Jiménez, E
dc.contributor.authorChristoforou, M
dc.contributor.authorPenfold, L
dc.contributor.authorCapece, D
dc.contributor.authorXiong, X
dc.contributor.authorMiao, Y
dc.contributor.authorParzych, K
dc.contributor.authorCaputo, VS
dc.contributor.authorSiskos, AP
dc.contributor.authorEncheva, V
dc.contributor.authorLiu, Z
dc.contributor.authorThiel, D
dc.contributor.authorKaiser, MF
dc.contributor.authorPiazza, P
dc.contributor.authorChaidos, A
dc.contributor.authorKaradimitris, A
dc.contributor.authorFranzoso, G
dc.contributor.authorSnijders, AP
dc.contributor.authorKeun, HC
dc.contributor.authorOyarzún, DA
dc.contributor.authorBarahona, M
dc.contributor.authorAuner, HW
dc.date.accessioned2021-05-11T11:04:29Z
dc.date.available2021-05-11T11:04:29Z
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2021, 118 (17)
dc.identifier.issn0027-8424
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4547
dc.identifier.eissn1091-6490
dc.identifier.eissn1091-6490en_US
dc.identifier.doi10.1073/pnas.2018229118
dc.identifier.doi10.1073/pnas.2018229118en_US
dc.description.abstractCancer cells can survive chemotherapy-induced stress, but how they recover from it is not known. Using a temporal multiomics approach, we delineate the global mechanisms of proteotoxic stress resolution in multiple myeloma cells recovering from proteasome inhibition. Our observations define layered and protracted programs for stress resolution that encompass extensive changes across the transcriptome, proteome, and metabolome. Cellular recovery from proteasome inhibition involved protracted and dynamic changes of glucose and lipid metabolism and suppression of mitochondrial function. We demonstrate that recovering cells are more vulnerable to specific insults than acutely stressed cells and identify the general control nonderepressable 2 (GCN2)-driven cellular response to amino acid scarcity as a key recovery-associated vulnerability. Using a transcriptome analysis pipeline, we further show that GCN2 is also a stress-independent bona fide target in transcriptional signature-defined subsets of solid cancers that share molecular characteristics. Thus, identifying cellular trade-offs tied to the resolution of chemotherapy-induced stress in tumor cells may reveal new therapeutic targets and routes for cancer therapy optimization.
dc.formatPrint
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleSystems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs.
dc.typeJournal Article
dcterms.dateAccepted2021-04-21
rioxxterms.versionAM
rioxxterms.versionofrecord10.1073/pnas.2018229118
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfProceedings of the National Academy of Sciences of the United States of America
pubs.issue17
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.publication-statusPublished
pubs.volume118en_US
pubs.embargo.termsNot known
icr.researchteamMyeloma Group
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorKaiser, Martinen


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/