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

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dc.citation.firstpage25161
dc.citation.issueNumber28
dc.citation.journalTitleOncotarget
dc.citation.lastpage25174
dc.citation.volumeNumber6
dc.contributor.authorJolly, Mohit Kumar
dc.contributor.authorJia, Dongya
dc.contributor.authorBoareto, Marcelo
dc.contributor.authorMani, Sendurai A.
dc.contributor.authorPienta, Kenneth J.
dc.contributor.authorBen-Jacob, Eshel
dc.contributor.authorLevine, Herbert
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2016-03-28T20:49:40Z
dc.date.available2016-03-28T20:49:40Z
dc.date.issued2015
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.
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.
dc.identifier.doihttp://dx.doi.org/10.18632/oncotarget.4629
dc.identifier.urihttps://hdl.handle.net/1911/88653
dc.language.isoeng
dc.publisherImpact Journals, LLC.
dc.rightsAll content, except where otherwise noted, is licensed under aﾠCreative Commons Attribution 3.0 License.ﾠ
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subject.keywordOVOL
dc.subject.keywordcancer stem cells
dc.subject.keywordmultistability
dc.subject.keywordpartial EMT
dc.subject.keywordstemness window
dc.titleCoupling the modules of EMT and stemness: A tunable ‘stemness window’ model
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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