Dataset Information

Quantitative phosphoproteomics analysis uncovers CDK1- and PAK2-mediated malignant signaling pathways in clear cell Renal Cell Carcinoma

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

DISEASE(S): Kidney Cancer

SUBMITTER: Aydanur Senturk

LAB HEAD: Nurhan Ozlu

PROVIDER: PXD028428 | Pride | 2023-03-10

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	AS_20181122_P2_phospho_F1_rep1.raw	Raw
	AS_20181122_P2_phospho_F1_rep2.raw	Raw
	AS_20181122_P2_phospho_F1_rep3.raw	Raw
	AS_20181122_P2_phospho_F2_rep1.raw	Raw
	AS_20181122_P2_phospho_F2_rep2.raw	Raw

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Quantitative Phosphoproteomics Analysis Uncovers PAK2- and CDK1-Mediated Malignant Signaling Pathways in Clear Cell Renal Cell Carcinoma.

Senturk Aydanur A Sahin Ayse T AT Armutlu Ayse A Kiremit Murat Can MC Acar Omer O Erdem Selcuk S Bagbudar Sidar S Esen Tarik T Ozlu Nurhan N

Molecular & cellular proteomics : MCP 20220921 11

Clear cell Renal Cell Carcinoma (ccRCC) is among the 10 most common cancers in both men and women 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 9000 were singly quantified. Our in-depth analysis reve ...[more]

PMID: 36152754

Publication: 1/2

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