PXD059674-1

PXD059674 is an original dataset announced via ProteomeXchange.

Title	Pancreatic cancer-intrinsic HuR regulates the pro-tumorigenic properties of extracellular vesicles
Description	Pancreatic ductal adenocarcinoma (PDAC) tumors contain chaotic vasculature that limits immune surveillance and promotes early events in the metastatic cascade. However, current antiangiogenic therapies have failed in PDAC, and it remains important to uncover mechanisms by which cancer cells signal to endothelial cells to increase angiogenesis. The tumor-intrinsic RNA-binding protein HuR (ELAVL1) plays an important role re-shaping the tumor microenvironment (TME) by regulating the stability and translation of cytokine encoding transcripts. PDAC-intrinsic HuR influenced endothelial cell function in the TME via extracellular vesicle (EV) signaling, an underexplored signaling axis in tumor progression. HuR knockout (KO) tumors had impaired growth in an immunocompetent mouse model, and that administering purified wildtype (WT) EVs increased tumor growth. Further, isobaric-labeling quantitative proteomics showed that PDAC EVs contained HuR-dependent cargos relating to endothelial cell function and angiogenesis. Treatment of endothelial cells with HuR WT EVs strongly increased the expression of genes involved in barrier function, endothelial cell development, and directly increased their migratory and tube forming functions. In an immunocompetent orthotopic mouse model of PDAC, HuR increased endothelial cell presence and sprouting, while decreasing ICAM-1 expression. When utilizing the PalmGRET genetic EV reporter, decreased ICAM-1 within WT tumors occurred in endothelial cells that had imported PDAC EVs, suggesting signaling that directly modulates endothelial cell behavior in vivo. Collectively, our data reveal a new role of HuR in EV signaling to endothelial cells, promoting angiogenesis while restricting endothelial cell leukocyte trafficking behavior.
HostingRepository	PRIDE
AnnounceDate	2025-08-09
AnnouncementXML	Submission_2025-08-08_18:18:24.199.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-11 16:20:28	ID requested
⏵ 1	2025-08-08 18:18:25	announced

10.1101/2025.02.07.632847;

Guo Y, Finan JM, Bartlett AQ, Sivagnanam S, Blise KE, Kirchberger N, Betre K, McCarthy GA, Hawthorne K, Chen C, Grossberg A, Xia Z, Coussens LM, Sears RC, Brody JR, Eil R, Post-transcriptional regulator HuR promotes immune evasion in pancreatic ductal adenocarcinoma. bioRxiv, ():(2025) [pubmed]

submitter keyword: Pancreatic cancer-intrinsic HuR regulates the pro-tumorigenic properties of extracellular vesicles

Jonathan R. Brody
contact affiliation	Knight Cancer Institute Oregon Health & Science University Portland, OR 97239 USA
contact email	brodyj@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
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/2025/08/PXD059674

PRIDE project URI

• PRIDE
  1. PXD059674
     1. Label: PRIDE project
     2. Name: Pancreatic cancer-intrinsic HuR regulates the pro-tumorigenic properties of extracellular vesicles