PXD028428

PXD028428 is an original dataset announced via ProteomeXchange.

Title	Quantitative phosphoproteomics analysis uncovers CDK1- and PAK2-mediated malignant signaling pathways in clear cell Renal Cell Carcinoma
Description	Clear cell Renal Cell Carcinoma (ccRCC) is among the 10 most common cancers and causes more than 140,000 deaths worldwide every year. In order to elucidate the underlying molecular mechanisms orchestrated by phosphorylation modifications, we performed a comprehensive quantitative phosphoproteomics characterization of ccRCC tumor and normal adjacent tissues. Here, we identified 16,253 phosphopeptides, of which more than 9,000 were quantified. Our in-depth analysis revealed 1,336 phosphopeptides to be differentially regulated between tumor and normal tissues. Moreover, our data reveals that significantly up-regulated phosphoproteins are associated with cytoskeletal re-organization which suggests migratory and invasive behavior of renal tumors. This is supported by a pronounced mesenchymal profile of ccRCC phosphorylation events. Our rigorous characterization of the renal phosphoproteome also revealed that both EGFR and VEGFR are the most important mediators of phospho signaling in RCC pathogenesis. Furthermore, we determined the kinases PAK2, CDK1, Erk1 and Erk2 to be master kinases that are responsible for phosphorylations of many substrates associated with cell proliferation, inflammation and migration. These master kinases are targetable by inhibitory FDA-approved drugs such as fostamatinib and minocycline, which can serve as novel therapeutic agents for ccRCC treatment.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:42:51.291.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aydanur Senturk
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; dimethylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 13:49:33	ID requested
1	2023-03-11 04:52:29	announced
2	2023-11-14 07:40:41	announced	2023-11-14: Updated project metadata.
⏵ 3	2023-11-14 08:42:59	announced	2023-11-14: Updated project metadata.

Senturk A, Sahin AT, Armutlu A, Kiremit MC, Acar O, Erdem S, Bagbudar S, Esen T, Tuncbag N, Ozlu N, Quantitative Proteomics Identifies Secreted Diagnostic Biomarkers as well as Tumor-Dependent Prognostic Targets for Clear Cell Renal Cell Carcinoma. Mol Cancer Res, 19(8):1322-1337(2021) [pubmed]

Senturk A, Sahin AT, Armutlu A, Kiremit MC, Acar O, Erdem S, Bagbudar S, Esen T, Ozlu N, Quantitative Phosphoproteomics Analysis Uncovers PAK2- and CDK1-Mediated Malignant Signaling Pathways in Clear Cell Renal Cell Carcinoma. Mol Cell Proteomics, 21(11):100417(2022) [pubmed]

submitter keyword: biomarkers, signaling pathways, drug targets, phosphoproteomics, Renal Cell Carcinoma

Nurhan Ozlu
contact affiliation	Koc University
contact email	nozlu@ku.edu.tr
lab head
Aydanur Senturk
contact affiliation	Koc University
contact email	asenturk16@ku.edu.tr
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/2023/03/PXD028428

PRIDE project URI

• PRIDE
  1. PXD028428
     1. Label: PRIDE project
     2. Name: Quantitative phosphoproteomics analysis uncovers CDK1- and PAK2-mediated malignant signaling pathways in clear cell Renal Cell Carcinoma