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PXD010254

PXD010254 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRegulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity
DescriptionThe ability of cancer cells to switch phenotype in response to a dynamic intra-tumor microenvironment is a major barrier to effective therapy. In melanoma, down-regulation of the lineage addiction oncogene MITF (Microphthalmia-associated transcription factor) is a hallmark of the proliferative-to-invasive phenotype switch. Yet how MITF promotes proliferation and suppresses invasion is poorly understood. Here we show that expression of the key lipogenic enzyme stearoyl-CoA desaturase (SCD) is activated by MITF, but suppressed by the stress-responsive transcription factor ATF4. SCD expression is required for MITF-positive melanoma cell proliferation,. By contrast, MITF-low cells express reduced levels of SCD and are insensitive to its inhibition, indicating that cell phenotype dictates response to drugs targeting lipid metabolism. Since SCD suppresses inflammatory signalling and ATF4 expression, the results identify a positive feedback-loop that can maintain an invasive phenotype, uncover a key role for MITF and ATF4 in metabolic reprograming, and reveal fatty acid composition as a driver of melanoma phenotype-switching.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:46:32.995.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRoman Fischer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-06-28 01:29:59ID requested
12019-11-19 15:47:33announced
22019-11-26 05:37:19announced2019-11-26: Updated project metadata.
32024-10-22 04:46:41announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.molcel.2019.10.014;
Vivas-Garc, í, a Y, Falletta P, Liebing J, Louphrasitthiphol P, Feng Y, Chauhan J, Scott DA, Glodde N, Chocarro-Calvo A, Bonham S, Osterman AL, Fischer R, Ronai Z, Garc, í, a-Jim, é, nez C, H, ö, lzel M, Goding CR, Lineage-Restricted Regulation of SCD and Fatty Acid Saturation by MITF Controls Melanoma Phenotypic Plasticity. Mol Cell, 77(1):120-137.e9(2020) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: MITF/ATF4/Stearoyl CoA desaturase/Melanoma/Phenotype-switching/Fatty acid saturation
Contact List
Roman Fischer
contact affiliationDiscovery Proteomics Facility, Oxford
contact emailroman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliationUniversity of Oxford
contact emailroman.fischer@ndm.ox.ac.uk
dataset submitter
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