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dc.contributor.authorJolly, Mohit Kumar
Jia, Dongya
Boareto, Marcelo
Mani, Sendurai A.
Pienta, Kenneth J.
Ben-Jacob, Eshel
Levine, Herbert
dc.date.accessioned 2016-03-28T20:49:40Z
dc.date.available 2016-03-28T20:49:40Z
dc.date.issued 2015
dc.identifier.citation Jolly, Mohit Kumar, Jia, Dongya, Boareto, Marcelo, et al.. "Coupling the modules of EMT and stemness: A tunable ‘stemness window’ model." Oncotarget, 6, no. 28 (2015) Impact Journals, LLC.: 25161-25174. http://dx.doi.org/10.18632/oncotarget.4629.
dc.identifier.urihttps://hdl.handle.net/1911/88653
dc.description.abstract Metastasis 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.language.iso eng
dc.publisher Impact Journals, LLC.
dc.rights All 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.title Coupling the modules of EMT and stemness: A tunable ‘stemness window’ model
dc.type Journal article
dc.contributor.funder National Science Foundation
dc.contributor.funder Cancer Prevention and Research Institute of Texas
dc.contributor.funder Tauber Family Funds
dc.contributor.funder Maguy-Glass Chair in Physics of Complex Systems, Tel Aviv University
dc.contributor.funder National Institutes of Health
dc.contributor.funder National Cancer Institute
dc.contributor.funder FAPESP
dc.citation.journalTitle Oncotarget
dc.contributor.org Center for Theoretical Biological Physics
dc.subject.keywordOVOL
cancer stem cells
multistability
partial EMT
stemness window
dc.citation.volumeNumber 6
dc.citation.issueNumber 28
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.18632/oncotarget.4629
dc.identifier.pmcid PMC4694822
dc.identifier.pmid 26317796
dc.identifier.grantID PHY-1427654 (National Science Foundation)
dc.identifier.grantID 5RO1CA155243 (National Institutes of Health)
dc.identifier.grantID U54CA143803 (National Cancer Institute)
dc.identifier.grantID CA163124 (National Cancer Institute)
dc.identifier.grantID CA093900 (National Cancer Institute)
dc.identifier.grantID CA143055 (National Cancer Institute)
dc.identifier.grantID 2013/14388-8 (FAPESP)
dc.type.publication publisher version
dc.citation.firstpage 25161
dc.citation.lastpage 25174


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All content, except where otherwise noted, is licensed under aᅠCreative Commons Attribution 3.0 License.ᅠ
Except where otherwise noted, this item's license is described as All content, except where otherwise noted, is licensed under aᅠCreative Commons Attribution 3.0 License.ᅠ