PXD010254 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Regulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:46:32.995.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Roman Fischer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-06-28 01:29:59 | ID requested | |
1 | 2019-11-19 15:47:33 | announced | |
2 | 2019-11-26 05:37:19 | announced | 2019-11-26: Updated project metadata. |
⏵ 3 | 2024-10-22 04:46:41 | announced | 2024-10-22: 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 affiliation | Discovery Proteomics Facility, Oxford |
contact email | roman.fischer@ndm.ox.ac.uk |
lab head | |
Roman Fischer |
contact affiliation | University of Oxford |
contact email | roman.fischer@ndm.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD010254
- Label: PRIDE project
- Name: Regulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity