PXD021542

PXD021542 is an original dataset announced via ProteomeXchange.

Title	Low endothelial cell FAK expression reduces pancreatic ductal adenocarcinoma liver metastasis after gemcitabine treatment
Description	Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a high level of liver metastasis. Despite substantial advances, resistance to therapy, including gemcitabine, is still a major obstacle to improved progression free survival. Recent studies have indicated that endothelial cell (EC) focal adhesion kinase (FAK) regulates DNA-damaging therapy induced angiocrine factors and chemosensitivity in malignant cells. However, the effect of EC-FAK regulated angiocrine signalling in chemosensitivity of metastatic PDAC remains unexplored. Here, we show that inducible loss of EC-FAK in both orthotopic and spontaneous mouse models of PDAC reduces liver metastasis and improves survival rates in gemcitabine treated, but not untreated, mice, without affecting primary tumour growth, tumour vascularization, blood vessel leakage or early metastatic events. Phosphoproteomics analysis show a downregulation of the MAPK/ RAF/ PAK signalling pathways in gemcitabine treated FAK-depleted ECs compared to gemcitabine treated WT ECs. Moreover, low levels of EC-FAK correlate with increased survival and reduced relapse in gemcitabine treated human PDAC patients, supporting the clinical relevance of our findings. Altogether, we have identified a new role of EC-FAK regulating PDAC liver metastasis upon gemcitabine treatment that impacts on survival.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:25:57.712.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021542
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Vinothini Rajeeve
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-17 08:37:06	ID requested
1	2023-03-10 15:45:50	announced
⏵ 2	2023-11-14 08:25:58	announced	2023-11-14: Updated project metadata.

10.6019/PXD021542;

Roy-Luzarraga M, Reynolds LE, de Lux, á, n-Delgado B, Maiques O, Wisniewski L, Newport E, Rajeeve V, Drake RJG, G, ó, mez-Escudero J, Richards FM, Weller C, Dormann C, Meng YM, Vermeulen PB, Saur D, Sanz-Moreno V, Wong PP, G, é, raud C, Cutillas PR, Hodivala-Dilke K, Suppression of Endothelial Cell FAK Expression Reduces Pancreatic Ductal Adenocarcinoma Metastasis after Gemcitabine Treatment. Cancer Res, 82(10):1909-1925(2022) [pubmed]

submitter keyword: Endothelium, Chemotherapy, Focal Adhesion Kinase, Tumour models, Resistance, Gemcitabine, phosphoproteomics, Metastasis,Pancreatic Ductal Adenocarcinoma, LC-MS/MS

Pedro R Cutillas
contact affiliation	Centre for Genomics and Computational Biology Barts Cancer Institute Queen Mary, University of London John Vane Science Centre, Charterhouse Square, London EC1M 6BQ Tel: +44 (0)20 7882 8266 | Fax: +44 (0)20 7882 3891 | Email: p.cutillas@qmul.ac.uk
contact email	p.cutillas@qmul.ac.uk
lab head
Vinothini Rajeeve
contact affiliation	Centre for Haemato Oncology
contact email	v.rajeeve@qmul.ac.uk
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/2023/03/PXD021542

PRIDE project URI

• PRIDE
  1. PXD021542
     1. Label: PRIDE project
     2. Name: Low endothelial cell FAK expression reduces pancreatic ductal adenocarcinoma liver metastasis after gemcitabine treatment