PXD028292

PXD028292 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of melanoma resistant cells transfected with siRNA targeting DDR2 or treated with DDR2 inhibitor or Dasatinib
Description	Combined therapy with anti-BRAF plus anti-MEK is currently used as first-line treatment of patients with metastatic melanomas harboring the somatic BRAF V600E mutation. However, the main issue with targeted therapy is the acquisition of tumor cell resistance. In 70% of resistant melanoma cells, the resistant process consists in epithelial-to-mesenchymal transition (EMT). This process called phenotype switching makes melanoma cells more invasive. Its signature is characterized by MITF low, AXL high, and actin cytoskeleton reorganization through RhoA activation. In parallel of this phenotype switching phase, the resistant cells exhibit an anarchic cell proliferation due to hyper-activation of the MAP kinase pathway. We show that a majority of human melanoma overexpress discoidin domain receptor 2 (DDR2) after treatment. The same result was found in resistant cell lines presenting phenotype switching compared to the corresponding sensitive cell lines. We demonstrate that DDR2 inhibition induces a decrease in AXL expression and reduces stress fiber formation in resistant melanoma cell lines. In this phenotype switching context, we report that DDR2 control cell and tumor proliferation through the MAP kinase pathway in resistant cells in vitro and in vivo. Therefore, inhibition of DDR2 could be a new and promising strategy for countering this resistance mechanism.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:45:22.132.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dupuy Jean-William
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:11:15	ID requested
1	2023-05-02 03:00:04	announced
⏵ 2	2023-11-14 08:45:30	announced	2023-11-14: Updated project metadata.

Sala M, Allain N, Moreau M, Jabouille A, Henriet E, Abou-Hammoud A, Uguen A, Di-Tommaso S, Dourthe C, Raymond AA, Dupuy JW, Gerard E, Dugot-Senant N, Rousseau B, Merlio JP, Pham-Ledart A, Vergier B, Tartare-Deckert S, Moreau V, Saltel F, Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation. Oncogene, 41(18):2571-2586(2022) [pubmed]

submitter keyword: resistance, quantitative proteome,Melanoma, discoidin domain receptors

Frédéric Saltel
contact affiliation	BaRITOn, Bordeaux Research in Translational Oncology, Team 1, 146 Rue Léo Saignat, Bordeaux, F-33076, France.
contact email	frederic.saltel@inserm.fr
lab head
Dupuy Jean-William
contact affiliation	Plateforme Proteome Bordeaux
contact email	jean-william.dupuy@u-bordeaux.fr
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/2023/05/PXD028292

PRIDE project URI

• PRIDE
  1. PXD028292
     1. Label: PRIDE project
     2. Name: Proteomic analysis of melanoma resistant cells transfected with siRNA targeting DDR2 or treated with DDR2 inhibitor or Dasatinib