Hysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability
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- dc.contributor.author Celià-Terrassa, Toni
- dc.contributor.author Bastian, Caleb
- dc.contributor.author Liu, Dan
- dc.contributor.author Ell, Brian
- dc.contributor.author Aiello, Nicole M.
- dc.contributor.author Wei, Yong
- dc.contributor.author Zamalloa, Jose
- dc.contributor.author Blanco, Andres M.
- dc.contributor.author Hang, Xiang
- dc.contributor.author Kunisky, Dmitriy
- dc.contributor.author Li, Wenyang
- dc.contributor.author Williams, Elizabeth D.
- dc.contributor.author Rabitz, Herschel
- dc.contributor.author Kang, Yibin
- dc.date.accessioned 2019-06-13T06:24:20Z
- dc.date.available 2019-06-13T06:24:20Z
- dc.date.issued 2018
- dc.description.abstract Epithelial-mesenchymal transition (EMT) have been extensively characterized in development and cancer, and its dynamics have been modeled as a non-linear process. However, less is known about how such dynamics may affect its biological impact. Here, we use mathematical modeling and experimental analysis of the TGF-β-induced EMT to reveal a non-linear hysteretic response of E-cadherin repression tightly controlled by the strength of the miR-200s/ZEBs negative feedback loop. Hysteretic EMT conveys memory state, ensures rapid and robust cellular response and enables EMT to persist long after withdrawal of stimuli. Importantly, while both hysteretic and non-hysteretic EMT confer similar morphological changes and invasive potential of cancer cells, only hysteretic EMT enhances lung metastatic colonization efficiency. Cells that undergo hysteretic EMT differentially express subsets of stem cell and extracellular matrix related genes with significant clinical prognosis value. These findings illustrate distinct biological impact of EMT depending on the dynamics of the transition.
- dc.format.mimetype application/pdf
- dc.identifier.citation Celià-Terrassa T, Bastian C, Liu DD, Ell B, Aiello NM, Wei Y. et al. Hysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability. Nat Commun. 2018 Nov 27;9(1):5005. DOI: 10.1038/s41467-018-07538-7
- dc.identifier.doi http://dx.doi.org/10.1038/s41467-018-07538-7
- dc.identifier.issn 2041-1723
- dc.identifier.uri http://hdl.handle.net/10230/41747
- dc.language.iso eng
- dc.publisher Nature Research
- dc.rights This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Histèresi
- dc.subject.other Metàstasi
- dc.title Hysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion