Boareto, MarceloJolly, Mohit KumarGoldman, AaronPietilä, MikaMani, Sendurai A.Sengupta, ShiladityaBen-Jacob, EshelLevine, HerbertOnuchic, Jose’ N.2016-07-142016Boareto, Marcelo, Mohit Kumar Jolly, Aaron Goldman, Mika Pietilä, Sendurai A. Mani, Shiladitya Sengupta, Eshel Ben-Jacob, Herbert Levine, and Jose’ N. Onuchic. 2016. “Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype.” Journal of the Royal Society Interface 13 (118): 20151106. doi:10.1098/rsif.2015.1106. http://dx.doi.org/10.1098/rsif.2015.1106.1742-5689http://nrs.harvard.edu/urn-3:HUL.InstRepos:27662180Metastasis 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.en-USNotch signallingepithelial–mesenchymal transitioncirculating tumour cellshybrid epithelial/mesenchymal phenotypemultistabilitycell–cell communicationJournal Article2016-07-1410.1098/rsif.2015.1106