PXD046026 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Quantitative secretomics identifies ligand-receptor pairs in pancreatic cancer that mediate bidirectional crosstalk between cancer stem cells and nociceptors |
Description | Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest and most metastatic cancers in human. PDACs respond poorly to therapies, partly due to cancer stem cells (CSCs) that self-renew, survive chemotherapies, metastasise and replenish the tumour. Factors secreted by tumour cells mediate autocrine/paracrine crosstalk with surrounding cells contributing to the stem cell niche but are still insufficiently characterised. Here we used quantitative SILAC proteomics to identify secreted factors enriched in CSC secretome compared to non-CSCs. Among them were GDF15 and VGF, factors involved in cachexia and pain stimuli. GDF15 and VGF promoted CSC self-renewal and growth through autocrine effects. TGFβ/Activin signalling lowered GDF15 and VGF expression via SMAD2/3-SMAD4-SNON, switching to ATF4-CREB-mediated induction upon cell stress. Co-culture of PDAC-CSCs and hESC-derived neural cells for mimicking cellular crosstalk in PDAC revealed that paracrine signalling via GDF15/VGF promoted nociceptor formation and neurite outgrowth. In turn, Substance P from neurons supported CSC self-renewal, EMT/migration and clonal evolution that was also impacted by SMAD4 genetic status. Lastly, the serum levels of GDF15 and VGF were elevated in PDAC patients suggesting their utility as biomarkers for PDAC detection. Collectively, our data uncovered that cachexia and pain signalling factors mediate the crosstalk between CSCs and nociceptors. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:35:20.980.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Svenja Hester |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | 4x(2)H labeled dimethylated L-lysine; 6x(13)C; 6x(13)C; deamidated residue; 6x(13)C labeled L-arginine; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-10-10 04:53:08 | ID requested | |
1 | 2024-10-07 13:50:37 | announced | |
⏵ 2 | 2024-10-22 06:35:21 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: VGF Nerve Growth Factor Inducible (VGF), Pancreatic cancer, Cancer stem cell (CSC), tumour growth, gemcitabine., transforming growth factor beta (TGFβ), Growth differentiation factor 15 (GDF15),Pancreatic adenocarcinoma (PDAC) |
Contact List
Dr. Siim Pauklin |
contact affiliation | Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Old Road, University of Oxford, Oxford OX3 7LD, UK |
contact email | siim.pauklin@ndorms.ox.ac.uk |
lab head | |
Svenja Hester |
contact affiliation | Nuffield Department of Medicine |
contact email | svenja.hester@ndm.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046026
- Label: PRIDE project
- Name: Quantitative secretomics identifies ligand-receptor pairs in pancreatic cancer that mediate bidirectional crosstalk between cancer stem cells and nociceptors