Implications of the hybrid epithelial/mesenchymal phenotype in metastasis

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dc.citation.journalTitleFrontiers in Oncologyen_US
dc.citation.volumeNumber5en_US
dc.contributor.authorJolly, Mohit Kumaren_US
dc.contributor.authorBoareto, Marceloen_US
dc.contributor.authorHuang, Binen_US
dc.contributor.authorJia, Dongyaen_US
dc.contributor.authorLu, Mingyangen_US
dc.contributor.authorBen-Jacob, Eshelen_US
dc.contributor.authorOnuchic, José Nelsonen_US
dc.contributor.authorLevine, Herberten_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.contributor.orgSystems, Synthetic, and Physical Biology Programen_US
dc.date.accessioned2016-03-24T18:24:34Zen_US
dc.date.available2016-03-24T18:24:34Zen_US
dc.date.issued2015en_US
dc.description.abstractTransitions between epithelial and mesenchymal phenotypes - the epithelial to -mesenchymal transition (EMT) and its reverse the mesenchymal to epithelial transition (MET) - are hallmarks of cancer metastasis. While transitioning between the epithelial and mesenchymal phenotypes, cells can also attain a hybrid epithelial/mesenchymal (E/M) (i.e., partial or intermediate EMT) phenotype. Cells in this phenotype have mixed epithelial (e.g., adhesion) and mesenchymal (e.g., migration) properties, thereby allowing them to move collectively as clusters. If these clusters reach the bloodstream intact, they can give rise to clusters of circulating tumor cells (CTCs), as have often been seen experimentally. Here, we review the operating principles of the core regulatory network for EMT/MET that acts as a "three-way" switch giving rise to three distinct phenotypes - E, M and hybrid E/M - and present a theoretical framework that can elucidate the role of many other players in regulating epithelial plasticity. Furthermore, we highlight recent studies on partial EMT and its association with drug resistance and tumor-initiating potential; and discuss how cell-cell communication between cells in a partial EMT phenotype can enable the formation of clusters of CTCs. These clusters can be more apoptosis-resistant and have more tumor-initiating potential than singly moving CTCs with a wholly mesenchymal (complete EMT) phenotype. Also, more such clusters can be formed under inflammatory conditions that are often generated by various therapies. Finally, we discuss the multiple advantages that the partial EMT or hybrid E/M phenotype have as compared to a complete EMT phenotype and argue that these collectively migrating cells are the primary "bad actors" of metastasis.en_US
dc.identifier.citationJolly, Mohit Kumar, Boareto, Marcelo, Huang, Bin, et al.. "Implications of the hybrid epithelial/mesenchymal phenotype in metastasis." <i>Frontiers in Oncology,</i> 5, (2015) Frontiers Media S.A.: http://dx.doi.org/10.3389/fonc.2015.00155.en_US
dc.identifier.doihttp://dx.doi.org/10.3389/fonc.2015.00155en_US
dc.identifier.urihttps://hdl.handle.net/1911/88644en_US
dc.language.isoengen_US
dc.publisherFrontiers Media S.A.en_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordcancer stem cellsen_US
dc.subject.keywordcancer systems biologyen_US
dc.subject.keywordcell-fate decisionsen_US
dc.subject.keywordintermediate EMTen_US
dc.subject.keywordpartial EMTen_US
dc.titleImplications of the hybrid epithelial/mesenchymal phenotype in metastasisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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