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FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration
Tumor cells exhibit two interconvertible modes of cell motility referred to as mesenchymal and amoeboid migration. Mesenchymal mode is characterized by elongated morphology that requires high GTPase Rac activation, whereas amoeboid mode is dependent on actomyosin contractility induced by Rho/Rho-ass...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521682/ https://www.ncbi.nlm.nih.gov/pubmed/23097497 http://dx.doi.org/10.1091/mbc.E12-04-0310 |
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author | Saito, Koji Ozawa, Yuta Hibino, Keisuke Ohta, Yasutaka |
author_facet | Saito, Koji Ozawa, Yuta Hibino, Keisuke Ohta, Yasutaka |
author_sort | Saito, Koji |
collection | PubMed |
description | Tumor cells exhibit two interconvertible modes of cell motility referred to as mesenchymal and amoeboid migration. Mesenchymal mode is characterized by elongated morphology that requires high GTPase Rac activation, whereas amoeboid mode is dependent on actomyosin contractility induced by Rho/Rho-associated protein kinase (ROCK) signaling. While elongated morphology is driven by Rac-induced protrusion at the leading edge, how Rho/ROCK signaling controls amoeboid movement is not well understood. We identified FilGAP, a Rac GTPase-activating protein (GAP), as a mediator of Rho/ROCK-dependent amoeboid movement of carcinoma cells. We show that depletion of endogenous FilGAP in carcinoma cells induced highly elongated mesenchymal morphology. Conversely, forced expression of FilGAP induced a round/amoeboid morphology that requires Rho/ROCK-dependent phosphorylation of FilGAP. Moreover, depletion of FilGAP impaired breast cancer cell invasion through extracellular matrices and reduced tumor cell extravasation in vivo. Thus phosphorylation of FilGAP by ROCK appears to promote amoeboid morphology of carcinoma cells, and FilGAP contributes to tumor invasion. |
format | Online Article Text |
id | pubmed-3521682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35216822013-03-02 FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration Saito, Koji Ozawa, Yuta Hibino, Keisuke Ohta, Yasutaka Mol Biol Cell Articles Tumor cells exhibit two interconvertible modes of cell motility referred to as mesenchymal and amoeboid migration. Mesenchymal mode is characterized by elongated morphology that requires high GTPase Rac activation, whereas amoeboid mode is dependent on actomyosin contractility induced by Rho/Rho-associated protein kinase (ROCK) signaling. While elongated morphology is driven by Rac-induced protrusion at the leading edge, how Rho/ROCK signaling controls amoeboid movement is not well understood. We identified FilGAP, a Rac GTPase-activating protein (GAP), as a mediator of Rho/ROCK-dependent amoeboid movement of carcinoma cells. We show that depletion of endogenous FilGAP in carcinoma cells induced highly elongated mesenchymal morphology. Conversely, forced expression of FilGAP induced a round/amoeboid morphology that requires Rho/ROCK-dependent phosphorylation of FilGAP. Moreover, depletion of FilGAP impaired breast cancer cell invasion through extracellular matrices and reduced tumor cell extravasation in vivo. Thus phosphorylation of FilGAP by ROCK appears to promote amoeboid morphology of carcinoma cells, and FilGAP contributes to tumor invasion. The American Society for Cell Biology 2012-12-15 /pmc/articles/PMC3521682/ /pubmed/23097497 http://dx.doi.org/10.1091/mbc.E12-04-0310 Text en © 2012 Saito et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Saito, Koji Ozawa, Yuta Hibino, Keisuke Ohta, Yasutaka FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration |
title | FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration |
title_full | FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration |
title_fullStr | FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration |
title_full_unstemmed | FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration |
title_short | FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration |
title_sort | filgap, a rho/rho-associated protein kinase–regulated gtpase-activating protein for rac, controls tumor cell migration |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521682/ https://www.ncbi.nlm.nih.gov/pubmed/23097497 http://dx.doi.org/10.1091/mbc.E12-04-0310 |
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