Proteomics

Dataset Information

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Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma


ABSTRACT: Aberrant tyrosine kinase activity can influence tumor growth and is regulated by phosphorylation. Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. We investigated phosphorylated kinases as target in PDAC. Mass spectrometry-based phosphoproteomic analysis was performed of PDAC cell lines to evaluate active kinases. Pathway analysis and inferred kinase activity was performed to identify novel targets. We investigated targeting of focal adhesion kinase in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Phosphoproteome analysis upon treatment was performed to evaluate signaling..PDAC cell lines portrayed high activity of multiple receptor tyrosine kinases. Non-receptor kinase, focal adhesion kinase (FAK), was identified in all cell lines by our phosphoproteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo. In conclusion, our study shows a high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pancreatic Ductal Cell

DISEASE(S): Pancreatic Ductal Adenocarcinoma

SUBMITTER: Sander Piersma  

LAB HEAD: Connie Jimenez

PROVIDER: PXD024548 | Pride | 2021-09-10

REPOSITORIES: pride

Dataset's files

Source:
Action DRS
Lysate_peptide_table.xlsx Xlsx
Lysate_protein_table.xlsx Xlsx
MaxQuant_Lysate_txt.zip Other
MaxQuant_pTyr_txtr.zip Other
Phosphopeptide_table.xlsx Xlsx
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Publications

Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma.

Le Large T Y S TYS   Bijlsma M F MF   El Hassouni B B   Mantini G G   Lagerweij T T   Henneman A A AA   Funel N N   Kok B B   Pham T V TV   de Haas R R   Morelli L L   Knol J C JC   Piersma S R SR   Kazemier G G   van Laarhoven H W M HWM   Giovannetti E E   Jimenez C R CR  

Journal of experimental & clinical cancer research : CR 20210309 1


<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC.<h4>Methods</h4>Mass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines was used to evaluate active kinases. Pathway analysis and inferred kinase activity analysis was performed to identify novel targets. Su  ...[more]

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