PXD005432

PXD005432 is an original dataset announced via ProteomeXchange.

Title	Proteomics identifies markers of MAPKi resistance offering new therapeutic strategies in melanoma- Cytoplasmic (cyt), nuclear (ne) and secreted (sn) proteins of MAPKi sensitive melanoma cells
Description	MAPK inhibitors (MAPKi) show outstanding clinical response rates in melanoma patients harbouring BRAF mutations, but resistance is common. High-throughput, subcellular proteome analyses at two different MS laboratories and RNA-seq on two panels of primary melanoma cells that were either sensitive or MAPKi resistant, revealed that only fifteen proteins were sufficient to discriminate between resistant and sensitive cells. The two proteins with the highest discriminatory power were PTRF and IGFBP7, both highly upregulated in the resistant cells. They were associated with epithelial-mesenchymal transition (EMT) and are mechanistically linked. Knock-out of PTRF revealed targets involved in lysosomal activation, endocytosis, pH regulation, EMT, TGFbeta signalling and cell migration and adhesion. In addition, immunohistochemistry on patient samples showed that PTRF and IGFBP7 expression levels were significant biomarkers of poor progression free survival under MAPKi treatment. A drug screen of MAPKi resistant cells using a 960-compound kinase modulator library identified two lead compounds that were effective in targeting MAPKi resistant cells.
HostingRepository	PRIDE
AnnounceDate	2019-07-23
AnnouncementXML	Submission_2019-07-23_08:21:14.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD005432
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christopher Gerner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	residues isobaric at 128.058578 Da; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-11-24 00:56:26	ID requested
⏵ 1	2019-07-23 08:21:14	announced

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: BRAF, MEK, melanoma, resistance, mass spectrometry, PTRF, IGFBP7

Christopher Gerner
contact affiliation	University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry
contact email	christopher.gerner@univie.ac.at
lab head
Christopher Gerner
contact affiliation	University of Vienna
contact email	christopher.gerner@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005432
     1. Label: PRIDE project
     2. Name: Proteomics identifies markers of MAPKi resistance offering new therapeutic strategies in melanoma- Cytoplasmic (cyt), nuclear (ne) and secreted (sn) proteins of MAPKi sensitive melanoma cells