PXD010683-1

PXD010683 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomics links the intermediate filament nestin to vemurafenib resistance in melanoma cell lines
Description	Targeted inhibition of mutated kinases using selective MAP kinase inhibitors in malignant melanoma often results in temporary improvement of the metastatic disease followed by rapid development of resistance. To gain insights in molecular processes that govern resistance, we performed SILAC-based quantitative proteomics profiling of vemurafenib-resistant and -sensitive melanoma cells. Among downregulated proteins in vemurafenib-resistant cell lines we detected multiple proteins involved in cytoskeletal organization and signaling, including the intermediate filament nestin, which was one of the most down-regulated proteins. Previous studies showed that nestin is expressed in various types of solid tumors and its abundance correlates with malignant phenotype of transformed cells. However, the role of nestin in cancer cells with regard to acquired resistance is still poorly understood. We performed CRISPR/Cas9 knockout of the nestin gene (NES) in vemurafenib-sensitive cells and showed that loss of nestin leads to increased cellular proliferation and colony formation upon treatment with BRAF and MEK inhibitors. Moreover, nestin depletion led to increased invasiveness and metalloproteinase activity similar to resistant phenotype of melanoma cells. Finally, phosphoproteome analysis revealed that nestin depletion influenced signaling through integrin and PI3K-Akt-mTOR pathways and led to increased focal adhesion kinase expression and phosphorylation. Taken together, our results reveal that nestin is associated with acquired vemurafenib resistance in melanoma cell lines.
HostingRepository	PRIDE
AnnounceDate	2019-05-14
AnnouncementXML	Submission_2019-05-14_02:40:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicolas Nalpas
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	2018-08-06 01:27:07	ID requested
⏵ 1	2019-05-14 02:40:28	announced
2	2024-10-22 04:51:57	announced	2024-10-22: Updated project metadata.

Schmitt M, Sinnberg T, Nalpas NC, Maass A, Schittek B, Macek B, Quantitative Proteomics Links the Intermediate Filament Nestin to Resistance to Targeted BRAF Inhibition in Melanoma Cells. Mol Cell Proteomics, 18(6):1096-1109(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: melanoma, drug resistance, cytoskeletal proteins, mass spectrometry

Boris Macek
contact affiliation	Chair, Quantitative Proteomics Director, Proteome Center Tuebingen Interfaculty Institute for Cell Biology University of Tuebingen Auf der Morgenstelle 15 72076 Tuebingen Germany
contact email	boris.macek@uni-tuebingen.de
lab head
Nicolas Nalpas
contact affiliation	Tuebingen University
contact email	nalpas.nicolas@gmail.com
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/2019/05/PXD010683

PRIDE project URI

• PRIDE
  1. PXD010683
     1. Label: PRIDE project
     2. Name: Quantitative proteomics links the intermediate filament nestin to vemurafenib resistance in melanoma cell lines