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dc.contributor.authorJolly, Mohit Kumar
Tripathi, Satyendra C.
Jia, Dongya
Mooney, Steven M.
Celiktas, Muge
Hanash, Samir M.
Mani, Sendurai A.
Pienta, Kenneth J.
Ben-Jacob, Eshel
Levine, Herbert
dc.date.accessioned 2016-06-06T16:48:22Z
dc.date.available 2016-06-06T16:48:22Z
dc.date.issued 2016
dc.identifier.citation Jolly, Mohit Kumar, Tripathi, Satyendra C., Jia, Dongya, et al.. "Stability of the hybrid epithelial/mesenchymal phenotype." Oncotarget, (2016) http://dx.doi.org/10.18632/oncotarget.8166.
dc.identifier.urihttp://hdl.handle.net/1911/90452
dc.description.abstract Epithelial-to-Mesenchymal Transition (EMT) and its reverse - Mesenchymal to Epithelial Transition (MET) - are hallmarks of cellular plasticity during embryonic development and cancer metastasis. During EMT, epithelial cells lose cell-cell adhesion and gain migratory and invasive traits either partially or completely, leading to a hybrid epithelial/mesenchymal (hybrid E/M) or a mesenchymal phenotype respectively. Mesenchymal cells move individually, but hybrid E/M cells migrate collectively as observed during gastrulation, wound healing, and the formation of tumor clusters detected as Circulating Tumor Cells (CTCs). Typically, the hybrid E/M phenotype has largely been tacitly assumed to be transient and 'metastable'. Here, we identify certain 'phenotypic stability factors' (PSFs) such as GRHL2 that couple to the core EMT decision-making circuit (miR-200/ZEB) and stabilize hybrid E/M phenotype. Further, we show that H1975 lung cancer cells can display a stable hybrid E/M phenotype and migrate collectively, a behavior that is impaired by knockdown of GRHL2 and another previously identified PSF - OVOL. In addition, our computational model predicts that GRHL2 can also associate hybrid E/M phenotype with high tumor-initiating potential, a prediction strengthened by the observation that the higher levels of these PSFs may be predictive of poor patient outcome. Finally, based on these specific examples, we deduce certain network motifs that can stabilize the hybrid E/M phenotype. Our results suggest that partial EMT, i.e. a hybrid E/M phenotype, need not be 'metastable', and strengthen the emerging notion that partial EMT, but not necessarily a complete EMT, is associated with aggressive tumor progression.
dc.language.iso eng
dc.rights All content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.title Stability of the hybrid epithelial/mesenchymal phenotype
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
dc.contributor.funder National Institutes of Health
dc.contributor.funder Rubenstein Family Foundation
dc.contributor.funder Canary Foundation
dc.contributor.funder National Cancer Institute
dc.citation.journalTitle Oncotarget
dc.contributor.org Center for Theoretical Biological Physics
dc.contributor.org Graduate Program in Systems, Synthetic and Physical Biology
dc.subject.keywordcancer stem cells
cell-fate decisions
epithelial-mesenchymal transition
multistability
partial EMT
dc.contributor.publisher Impact Journals, LLC
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.18632/oncotarget.8166
dc.identifier.pmid 27008704
dc.identifier.grantID PHY-1427654 (National Science Foundation)
dc.identifier.grantID DMS-1361411 (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.type.publication publisher version


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All content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
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