PXD010254

PXD010254 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biomedical

submitter keyword: MITF/ATF4/Stearoyl CoA desaturase/Melanoma/Phenotype-switching/Fatty acid saturation

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/11/PXD010254

PRIDE project URI

• PRIDE
  1. PXD010254
     1. Label: PRIDE project
     2. Name: Regulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity