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PXD028297 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleBRAF activation by metabolic stress promotes glycolysis and survival, sensitizing NRASQ61 mutated melanomas to targeted therapy.
DescriptionNRAS-mutated melanoma lacks an approved first-line treatment. Metabolic reprogramming is considered a novel target to control cancer; however, it is mostly unknow how the NRAS oncogene contributes to this cancer hallmark. Here, we show that NRASQ61-mutated melanomas harbor specific metabolic alterations that render cells sensitive to sorafenib upon metabolic stress. Mechanistically, these cells seem to depend on glucose metabolism, as glucose deprivation promotes the switch of the RAF isoform used from CRAF to BRAF. This process contributes to cell survival and sustains glucose metabolism through the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2/6- phosphofructo-2-kinase/fructose-2,6-bisphosph 3 (PFKFB2/PFKFB3) heterodimers by BRAF. In turn, this phosphorylation favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop linking glycolysis and the RAS signaling pathway. In vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with the combination of 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence of the contributions of NRAS oncogenes to metabolic rewiring and proof of principle for the treatment of NRAS-mutated melanoma with combinations of metabolic stress (glycolysis inhibitors) and already approved drugs such as sorafenib.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-09-09 08:19:34ID requested
12023-01-09 07:45:23announced
Publication List
McGrail K, Granado-Mart, í, nez P, Esteve-Puig R, Garc, í, a-Ortega S, Ding Y, S, á, nchez-Redondo S, Ferrer B, Hernandez-Losa J, Canals F, Manzano A, Navarro-Sabat, é A, Bartrons R, Yanes O, P, é, rez-Alea M, Mu, ñ, oz-Couselo E, Garcia-Patos V, Recio JA, -mutated melanomas to targeted therapy. Nat Commun, 13(1):7113(2022) [pubmed]
Keyword List
submitter keyword: Melanoma
NRAS mutation
Metabolic stress
Contact List
Juan ÁngelRecio
contact affiliationBiomedical Research in Melanoma-Animal Models and Cancer Laboratory Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Hospital Barcelona-UAB Barcelona, 08035, Spain.
contact emailjuan.recio@vhir.org
lab head
contact affiliationVall Hebron Institute of Oncology
contact emailfcanals@vhio.net
dataset submitter
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