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Hysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability

Author

Listed:
  • Toni Celià-Terrassa

    (Princeton University
    Cancer Program, IMIM (Hospital del Mar Medical Research Institute))

  • Caleb Bastian

    (Princeton University)

  • Daniel D. Liu

    (Princeton University)

  • Brian Ell

    (Princeton University)

  • Nicole M. Aiello

    (Princeton University)

  • Yong Wei

    (Princeton University)

  • Jose Zamalloa

    (Princeton University
    Princeton University)

  • Andres M. Blanco

    (Princeton University)

  • Xiang Hang

    (Princeton University)

  • Dmitriy Kunisky

    (Princeton University)

  • Wenyang Li

    (Princeton University)

  • Elizabeth D. Williams

    (Queensland University of Technology (QUT), Translational Research Institute)

  • Herschel Rabitz

    (Princeton University
    Princeton University)

  • Yibin Kang

    (Princeton University)

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.

Suggested Citation

  • Toni Celià-Terrassa & Caleb Bastian & Daniel D. Liu & Brian Ell & Nicole M. Aiello & Yong Wei & Jose Zamalloa & Andres M. Blanco & Xiang Hang & Dmitriy Kunisky & Wenyang Li & Elizabeth D. Williams & H, 2018. "Hysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07538-7
    DOI: 10.1038/s41467-018-07538-7
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    Cited by:

    1. Helen F. McCreery & Georgina Gemayel & Ana Isabel Pais & Simon Garnier & Radhika Nagpal, 2022. "Hysteresis stabilizes dynamic control of self-assembled army ant constructions," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Steffen Plunder & Cathy Danesin & Bruno Glise & Marina A. Ferreira & Sara Merino-Aceituno & Eric Theveneau, 2024. "Modelling variability and heterogeneity of EMT scenarios highlights nuclear positioning and protrusions as main drivers of extrusion," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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