biostudies-literatureCelia-Terrassa TNIDCR NIH HHSNCI NIH HHS5005https://www.ebi.ac.uk/biostudies/studies/S-EPMC6258667biostudies-literatureUnknown9(1)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 cNature communicationsHysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability.PMC6258667R01 CA141062R01 CA198280K08 DE021430P30 CA072720Liu DDAiello NMWei YHang XKang YLi WWilliams EDRabitz HBlanco AMBastian CCelia-Terrassa TKunisky DEll BZamalloa JfalseHysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability.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 c2018-01-01T00:00:00Z2018 Nov2026-05-05T21:30:13.977Z2026-04-07T21:59:57.79ZS-EPMC62586673047934510.1038/s41467-018-07538-7