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    Implications of the hybrid epithelial/mesenchymal phenotype in metastasis

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    Author
    Jolly, Mohit Kumar; Boareto, Marcelo; Huang, Bin; Jia, Dongya; Lu, Mingyang; More... Ben-Jacob, Eshel; Onuchic, José N.; Levine, Herbert Less...
    Date
    2015
    Abstract
    Transitions 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.
    Citation
    Jolly, Mohit Kumar, Boareto, Marcelo, Huang, Bin, et al.. "Implications of the hybrid epithelial/mesenchymal phenotype in metastasis." Frontiers in Oncology, 5, (2015) Frontiers Media S.A.: http://dx.doi.org/10.3389/fonc.2015.00155.
    Published Version
    http://dx.doi.org/10.3389/fonc.2015.00155
    Keyword
    cancer stem cells; cancer systems biology; cell-fate decisions; intermediate EMT; partial EMT
    Type
    Journal article
    Publisher
    Frontiers Media S.A.
    Citable link to this page
    https://hdl.handle.net/1911/88644
    Rights
    This 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.
    Link to License
    http://creativecommons.org/licenses/by/4.0/
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    Managed by the Digital Scholarship Services at Fondren Library, Rice University
    Physical Address: 6100 Main Street, Houston, Texas 77005
    Mailing Address: MS-44, P.O.BOX 1892, Houston, Texas 77251-1892
    Site Map