PXD046026-1

PXD046026 is an original dataset announced via ProteomeXchange.

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	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:50:37.529.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

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.

Dataset with its publication pending

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)

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

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PRIDE project URI

• PRIDE
  1. PXD046026
     1. Label: PRIDE project
     2. Name: Quantitative secretomics identifies ligand-receptor pairs in pancreatic cancer that mediate bidirectional crosstalk between cancer stem cells and nociceptors