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MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion
Entosis is a nonapoptotic form of cell death initiated by actomyosin-dependent homotypic cell-in-cell invasion that can be observed in malignant exudates during tumor progression. We previously demonstrated formin-mediated actin dynamics at the rear of the invading cell as well as nonapoptotic plasm...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626544/ https://www.ncbi.nlm.nih.gov/pubmed/28774893 http://dx.doi.org/10.1083/jcb.201702010 |
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author | Hinojosa, Laura Soto Holst, Manuel Baarlink, Christian Grosse, Robert |
author_facet | Hinojosa, Laura Soto Holst, Manuel Baarlink, Christian Grosse, Robert |
author_sort | Hinojosa, Laura Soto |
collection | PubMed |
description | Entosis is a nonapoptotic form of cell death initiated by actomyosin-dependent homotypic cell-in-cell invasion that can be observed in malignant exudates during tumor progression. We previously demonstrated formin-mediated actin dynamics at the rear of the invading cell as well as nonapoptotic plasma membrane (PM) blebbing in this cellular motile process. Although the contractile actin cortex involved in bleb-driven motility is well characterized, a role for transcriptional regulation in this process has not been studied. Here, we explore the impact of the actin-controlled MRTF–SRF (myocardin-related transcription factor–serum response factor) pathway for sustained PM blebbing and entotic invasion. We find that cortical blebbing is tightly coupled to MRTF nuclear shuttling to promote the SRF transcriptional activity required for entosis. Furthermore, PM blebbing triggered SRF-mediated up-regulation of the metastasis-associated ERM protein Ezrin. Notably, Ezrin is sufficient and important to sustain bleb dynamics for cell-in-cell invasion when SRF is suppressed. Our results highlight the critical role of the actin-regulated MRTF transcriptional pathway for bleb-associated invasive motility, such as during entosis. |
format | Online Article Text |
id | pubmed-5626544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-56265442018-04-02 MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion Hinojosa, Laura Soto Holst, Manuel Baarlink, Christian Grosse, Robert J Cell Biol Research Articles Entosis is a nonapoptotic form of cell death initiated by actomyosin-dependent homotypic cell-in-cell invasion that can be observed in malignant exudates during tumor progression. We previously demonstrated formin-mediated actin dynamics at the rear of the invading cell as well as nonapoptotic plasma membrane (PM) blebbing in this cellular motile process. Although the contractile actin cortex involved in bleb-driven motility is well characterized, a role for transcriptional regulation in this process has not been studied. Here, we explore the impact of the actin-controlled MRTF–SRF (myocardin-related transcription factor–serum response factor) pathway for sustained PM blebbing and entotic invasion. We find that cortical blebbing is tightly coupled to MRTF nuclear shuttling to promote the SRF transcriptional activity required for entosis. Furthermore, PM blebbing triggered SRF-mediated up-regulation of the metastasis-associated ERM protein Ezrin. Notably, Ezrin is sufficient and important to sustain bleb dynamics for cell-in-cell invasion when SRF is suppressed. Our results highlight the critical role of the actin-regulated MRTF transcriptional pathway for bleb-associated invasive motility, such as during entosis. The Rockefeller University Press 2017-10-02 /pmc/articles/PMC5626544/ /pubmed/28774893 http://dx.doi.org/10.1083/jcb.201702010 Text en © 2017 Soto Hinojosa et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Hinojosa, Laura Soto Holst, Manuel Baarlink, Christian Grosse, Robert MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion |
title | MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion |
title_full | MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion |
title_fullStr | MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion |
title_full_unstemmed | MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion |
title_short | MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion |
title_sort | mrtf transcription and ezrin-dependent plasma membrane blebbing are required for entotic invasion |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626544/ https://www.ncbi.nlm.nih.gov/pubmed/28774893 http://dx.doi.org/10.1083/jcb.201702010 |
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