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PXD008276 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCancer Associated Fibroblast-FAK regulates malignant cell metabolism
DescriptionBreast and pancreatic cancers are characterised by profound metabolic changes1,2. Until recently, these changes have been ascribed to their intrinsic genetic profiles2-4. However, the contribution of cancer-associated fibroblasts (CAFs) to cell metabolism has not been fully investigated5. Here, we provide clinical evidence that reduction in stromal Focal Adhesion Kinase (FAK) correlates with reduced overall survival in human breast and pancreatic cancer patients. To model this, we developed FSP-Cre+;FAKfl/fl mice where FAK was deleted in a subpopulation of CAFs. We establish that loss of CAF-FAK is sufficient to enhance tumour growth without affecting desmoplasia in orthotopically injected breast and pancreatic carcinomas. Additionally, deletion of CAF-FAK enhances disease progression in the MMTV-PyMT spontaneous model of breast cancer. Furthermore, despite this pro-tumourigenic effect, a significant reduction in tumour angiogenesis was observed in late-stage tumours, but not early-stage, size-matched tumours in FSP-Cre+;FAKfl/fl mice. This indicates that loss of CAF-FAK is sufficient to reduce malignant cell dependency on blood vessel support suggesting acquired metabolic alterations in cancer cells. Indeed, 18F-FDG-PET imaging and glucose flux analysis revealed enhanced glucose catabolism in early-stage, size-matched tumours in FSP-Cre+;FAKfl/fl mice in vivo. Mechanistically, we demonstrate that conditioned medium from FAK-null CAFs enhances glycolysis and glycolytic capacity in malignant cells. Proteomics and phosphoproteomics analysis reveal enriched cytokine-mediated signalling pathways in FAK-null CAFs and subsequent enrichment of associated phosphopeptides in malignant cells, respectively. Overall, our data uncover a novel mechanism by which cytokines, regulated by CAF-FAK, can promote cancer growth and progression, and identify a new set of CAF-derived targets to interfere with cancer metabolism.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterPedro Casado-Izquierdo
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; deaminated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-11-23 01:17:11ID requested
12020-02-18 03:23:05announced
Publication List
Dataset with its publication pending
Keyword List
curator keyword: Biomedical
submitter keyword: FAK, Fibroblast, Metabolism
Contact List
Pedro R. Cutillas
contact affiliationCentre for Haemato-oncology, Barts Cancer Institute, Queen Mary University of London, London, EC1M6BQ, UK
contact emailp.cutillas@qmul.ac.uk
lab head
Pedro Casado-Izquierdo
contact affiliationCell Signalling
contact emailp.m.casado-izquierdo@qmul.ac.uk
dataset submitter
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