Coupling the modules of EMT and stemness: A tunable ‘stemness window’ model

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dc.citation.firstpage25161en_US
dc.citation.issueNumber28en_US
dc.citation.journalTitleOncotargeten_US
dc.citation.lastpage25174en_US
dc.citation.volumeNumber6en_US
dc.contributor.authorJolly, Mohit Kumaren_US
dc.contributor.authorJia, Dongyaen_US
dc.contributor.authorBoareto, Marceloen_US
dc.contributor.authorMani, Sendurai A.en_US
dc.contributor.authorPienta, Kenneth J.en_US
dc.contributor.authorBen-Jacob, Eshelen_US
dc.contributor.authorLevine, Herberten_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2016-03-28T20:49:40Zen_US
dc.date.available2016-03-28T20:49:40Zen_US
dc.date.issued2015en_US
dc.description.abstractMetastasis of carcinoma involves migration of tumor cells to distant organs and initiate secondary tumors. Migration requires a complete or partial Epithelial-to-Mesenchymal Transition (EMT), and tumor-initiation requires cells possessing stemness. Epithelial cells (E) undergoing a complete EMT to become mesenchymal (M) have been suggested to be more likely to possess stemness. However, recent studies suggest that stemness can also be associated with cells undergoing a partial EMT (hybrid E/M phenotype). Therefore, the correlation between EMT and stemness remains elusive. Here, using a theoretical framework that couples the core EMT and stemness modules (miR-200/ZEB and LIN28/let-7), we demonstrate that the positioning of 'stemness window' on the 'EMT axis' need not be universal; rather it can be fine-tuned. Particularly, we present OVOL as an example of a modulating factor that, due to its coupling with miR-200/ZEB/LIN28/let-7 circuit, fine-tunes the EMT-stemness interplay. Coupling OVOL can inhibit the stemness likelihood of M and elevate that of the hybrid E/M (partial EMT) phenotype, thereby pulling the 'stemness window' away from the M end of 'EMT axis'. Our results unify various apparently contradictory experimental findings regarding the interconnection between EMT and stemness, corroborate the emerging notion that partial EMT associates with stemness, and offer new testable predictions.en_US
dc.identifier.citationJolly, Mohit Kumar, Jia, Dongya, Boareto, Marcelo, et al.. "Coupling the modules of EMT and stemness: A tunable ‘stemness window’ model." <i>Oncotarget,</i> 6, no. 28 (2015) Impact Journals, LLC.: 25161-25174. http://dx.doi.org/10.18632/oncotarget.4629.en_US
dc.identifier.doihttp://dx.doi.org/10.18632/oncotarget.4629en_US
dc.identifier.urihttps://hdl.handle.net/1911/88653en_US
dc.language.isoengen_US
dc.publisherImpact Journals, LLC.en_US
dc.rightsAll content, except where otherwise noted, is licensed under aﾠCreative Commons Attribution 3.0 License.ﾠen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.subject.keywordOVOLen_US
dc.subject.keywordcancer stem cellsen_US
dc.subject.keywordmultistabilityen_US
dc.subject.keywordpartial EMTen_US
dc.subject.keywordstemness windowen_US
dc.titleCoupling the modules of EMT and stemness: A tunable ‘stemness window’ modelen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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