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dc.contributor.authorShorthouse, David
dc.contributor.authorRiedel, Angela
dc.contributor.authorKerr, Emma
dc.contributor.authorPedro, Luisa
dc.contributor.authorBihary, Dóra
dc.contributor.authorSamarajiwa, Shamith
dc.contributor.authorMartins, Carla P
dc.contributor.authorShields, Jacqueline
dc.contributor.authorHall, Benjamin A
dc.date.accessioned2018-10-18T10:21:53Z
dc.date.available2018-10-18T10:21:53Z
dc.date.issued2018-08-01
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284139
dc.description.abstractOsmotic regulation is a vital homoeostatic process in all cells and tissues. Cells initially respond to osmotic stresses by activating transmembrane transport proteins to move osmotically active ions. Disruption of ion and water transport is frequently observed in cellular transformations such as cancer. We report that genes involved in membrane transport are significantly deregulated in many cancers, and that their expression can distinguish cancer cells from normal cells with a high degree of accuracy. We present an executable model of osmotic regulation and membrane transport in mammalian cells, providing a mechanistic explanation for phenotype change in varied disease states, and accurately predicting behaviour from single cell expression data. We also predict key proteins involved in cellular transformation, SLC4A3 (AE3), and SLC9A1 (NHE1). Furthermore, we predict and verify a synergistic drug combination in vitro, of sodium and chloride channel inhibitors, which target the osmoregulatory network to reduce cancer-associated phenotypes in fibroblasts.
dc.description.sponsorshipRoyal Society, MRC
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectFibroblasts
dc.subjectStromal Cells
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectBiological Transport
dc.subjectPhenotype
dc.subjectModels, Biological
dc.subjectEmbryo, Mammalian
dc.subjectOsmoregulation
dc.titleExploring the role of stromal osmoregulation in cancer and disease using executable modelling.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameNat Commun
prism.startingPage3011
prism.volume9
dc.identifier.doi10.17863/CAM.31510
dcterms.dateAccepted2018-06-29
rioxxterms.versionofrecord10.1038/s41467-018-05414-y
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08
dc.contributor.orcidShorthouse, David [0000-0002-3207-3584]
dc.contributor.orcidSamarajiwa, Shamith [0000-0003-1046-0601]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idRoyal Society (Paul Instrument Fund) (UF130039)
pubs.funder-project-idMRC (unknown)
pubs.funder-project-idMedical Research Council (MC_UU_12022/9)
pubs.funder-project-idMRC (MR/N501876/1)
pubs.funder-project-idMRC
pubs.funder-project-idCancer Research UK (CB4160)
pubs.funder-project-idMedical Research Council (MC_UU_12022/5)
pubs.funder-project-idMRC (MC_UU_12022/10)
cam.issuedOnline2018-08


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International