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The activation of INF2 by Piezo1/Ca(2+) is required for mesenchymal to amoeboid transition in confined environments
To invade heterogenous tissues, transformed cells may undergo a mesenchymal to amoeboid transition (MAT). However, the molecular mechanisms regulating this transition are poorly defined. In invasive melanoma cells, we demonstrate that intracellular [Ca(2+)] increases with the degree of confinement i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10515767/ https://www.ncbi.nlm.nih.gov/pubmed/37745412 http://dx.doi.org/10.1101/2023.06.23.546346 |
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author | Kar, Neelakshi Caruso, Alexa P. Prokopiou, Nicos Logue, Jeremy S. |
author_facet | Kar, Neelakshi Caruso, Alexa P. Prokopiou, Nicos Logue, Jeremy S. |
author_sort | Kar, Neelakshi |
collection | PubMed |
description | To invade heterogenous tissues, transformed cells may undergo a mesenchymal to amoeboid transition (MAT). However, the molecular mechanisms regulating this transition are poorly defined. In invasive melanoma cells, we demonstrate that intracellular [Ca(2+)] increases with the degree of confinement in a Piezo1 dependent fashion. Moreover, Piezo1/Ca(2+) is found to drive amoeboid and not mesenchymal migration in confined environments. Consistent with a model in which Piezo1 senses tension at the plasma membrane, the percentage of cells using amoeboid migration is further increased in undulating microchannels. Surprisingly, amoeboid migration was not promoted by myosin light chain kinase (MLCK), which is sensitive to intracellular [Ca(2+)]. Instead, we report that Piezo1/Ca(2+) activates inverted formin-2 (INF2) to induce widespread actin cytoskeletal remodeling. Strikingly, the activation of INF2 is found to promote de-adhesion, which in turn facilitates MAT. Using micropatterned surfaces, we demonstrate that cells require INF2 to effectively migrate in environments with challenging mechanochemical properties. |
format | Online Article Text |
id | pubmed-10515767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-105157672023-09-23 The activation of INF2 by Piezo1/Ca(2+) is required for mesenchymal to amoeboid transition in confined environments Kar, Neelakshi Caruso, Alexa P. Prokopiou, Nicos Logue, Jeremy S. bioRxiv Article To invade heterogenous tissues, transformed cells may undergo a mesenchymal to amoeboid transition (MAT). However, the molecular mechanisms regulating this transition are poorly defined. In invasive melanoma cells, we demonstrate that intracellular [Ca(2+)] increases with the degree of confinement in a Piezo1 dependent fashion. Moreover, Piezo1/Ca(2+) is found to drive amoeboid and not mesenchymal migration in confined environments. Consistent with a model in which Piezo1 senses tension at the plasma membrane, the percentage of cells using amoeboid migration is further increased in undulating microchannels. Surprisingly, amoeboid migration was not promoted by myosin light chain kinase (MLCK), which is sensitive to intracellular [Ca(2+)]. Instead, we report that Piezo1/Ca(2+) activates inverted formin-2 (INF2) to induce widespread actin cytoskeletal remodeling. Strikingly, the activation of INF2 is found to promote de-adhesion, which in turn facilitates MAT. Using micropatterned surfaces, we demonstrate that cells require INF2 to effectively migrate in environments with challenging mechanochemical properties. Cold Spring Harbor Laboratory 2023-10-21 /pmc/articles/PMC10515767/ /pubmed/37745412 http://dx.doi.org/10.1101/2023.06.23.546346 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Kar, Neelakshi Caruso, Alexa P. Prokopiou, Nicos Logue, Jeremy S. The activation of INF2 by Piezo1/Ca(2+) is required for mesenchymal to amoeboid transition in confined environments |
title | The activation of INF2 by Piezo1/Ca(2+) is required for mesenchymal to amoeboid transition in confined environments |
title_full | The activation of INF2 by Piezo1/Ca(2+) is required for mesenchymal to amoeboid transition in confined environments |
title_fullStr | The activation of INF2 by Piezo1/Ca(2+) is required for mesenchymal to amoeboid transition in confined environments |
title_full_unstemmed | The activation of INF2 by Piezo1/Ca(2+) is required for mesenchymal to amoeboid transition in confined environments |
title_short | The activation of INF2 by Piezo1/Ca(2+) is required for mesenchymal to amoeboid transition in confined environments |
title_sort | activation of inf2 by piezo1/ca(2+) is required for mesenchymal to amoeboid transition in confined environments |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10515767/ https://www.ncbi.nlm.nih.gov/pubmed/37745412 http://dx.doi.org/10.1101/2023.06.23.546346 |
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