Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype

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dc.citation.issueNumber118
dc.citation.journalTitleJournal of the Royal Society Interface
dc.citation.volumeNumber13
dc.contributor.authorBoareto, Marcelo
dc.contributor.authorJolly, Mohit Kumar
dc.contributor.authorGoldman, Aaron
dc.contributor.authorPietilä, Mika
dc.contributor.authorMani, Sendurai A.
dc.contributor.authorSengupta, Shiladitya
dc.contributor.authorBen-Jacob, Eshel
dc.contributor.authorLevine, Herbert
dc.contributor.authorOnuchic, José Nelson
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2016-07-07T21:09:20Z
dc.date.available2016-07-07T21:09:20Z
dc.date.issued2016
dc.description.abstractMetastasis can involve repeated cycles of epithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition. Cells can also undergo partial transitions to attain a hybrid epithelial/mesenchymal (E/M) phenotype that allows the migration of adhering cells to form a cluster of circulating tumour cells. These clusters can be apoptosis-resistant and possess an increased metastatic propensity as compared to the cells that undergo a complete EMT (mesenchymal cells). Hence, identifying the key players that can regulate the formation and maintenance of such clusters may inform anti-metastasis strategies. Here, we devise a mechanism-based theoretical model that links cell–cell communication via Notch-Delta-Jagged signalling with the regulation of EMT. We demonstrate that while both Notch-Delta and Notch-Jagged signalling can induce EMT in a population of cells, only Jagged-dominated Notch signalling, but not Delta-dominated signalling, can lead to the formation of clusters containing hybrid E/M cells. Our results offer possible mechanistic insights into the role of Jagged in tumour progression, and offer a framework to investigate the effects of other microenvironmental signals during metastasis.
dc.identifier.citationBoareto, Marcelo, Jolly, Mohit Kumar, Goldman, Aaron, et al.. "Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype." <i>Journal of the Royal Society Interface,</i> 13, no. 118 (2016) Royal Society Publishing: http://dx.doi.org/10.1098/rsif.2015.1106.
dc.identifier.doihttp://dx.doi.org/10.1098/rsif.2015.1106
dc.identifier.urihttps://hdl.handle.net/1911/90841
dc.language.isoeng
dc.publisherRoyal Society Publishing
dc.rightsPublished by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.keywordnotch signaling
dc.subject.keywordepithelial–mesenchymal transition
dc.subject.keywordcirculating tumour cells
dc.subject.keywordhybrid epithelial/mesenchymal phenotype
dc.subject.keywordmultistability
dc.subject.keywordcell–cell communication
dc.titleNotch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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