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Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling

BACKGROUND: Although there is extensive evidence for the amoeboid invasiveness of cancer cells in vitro, much less is known about the role of amoeboid invasiveness in metastasis and the importance of Rho/ROCK/MLC signaling in this process. RESULTS: We analyzed the dependence of amoeboid invasiveness...

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Autores principales: Kosla, Jan, Paňková, Daniela, Plachý, Jiří, Tolde, Ondřej, Bicanová, Kristýna, Dvořák, Michal, Rösel, Daniel, Brábek, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735423/
https://www.ncbi.nlm.nih.gov/pubmed/23899007
http://dx.doi.org/10.1186/1478-811X-11-51
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author Kosla, Jan
Paňková, Daniela
Plachý, Jiří
Tolde, Ondřej
Bicanová, Kristýna
Dvořák, Michal
Rösel, Daniel
Brábek, Jan
author_facet Kosla, Jan
Paňková, Daniela
Plachý, Jiří
Tolde, Ondřej
Bicanová, Kristýna
Dvořák, Michal
Rösel, Daniel
Brábek, Jan
author_sort Kosla, Jan
collection PubMed
description BACKGROUND: Although there is extensive evidence for the amoeboid invasiveness of cancer cells in vitro, much less is known about the role of amoeboid invasiveness in metastasis and the importance of Rho/ROCK/MLC signaling in this process. RESULTS: We analyzed the dependence of amoeboid invasiveness of rat and chicken sarcoma cells and the metastatic activity of chicken cells on individual elements of the Rho/ROCK/MLC pathway. In both animal models, inhibition of Rho, ROCK or MLC resulted in greatly decreased cell invasiveness in vitro, while inhibition of extracellular proteases using a broad spectrum inhibitor did not have a significant effect. The inhibition of both Rho activity and MLC phosphorylation by dominant negative mutants led to a decreased capability of chicken sarcoma cells to metastasize. Moreover, the overexpression of RhoA in non-metastatic chicken cells resulted in the rescue of both invasiveness and metastatic capability. Rho and ROCK, unlike MLC, appeared to be directly involved in the maintenance of the amoeboid phenotype, as their inhibition resulted in the amoeboid-mesenchymal transition in analyzed cell lines. CONCLUSION: Taken together, these results suggest that protease-independent invasion controlled by elements of the Rho/ROCK/MLC pathway can be frequently exploited by metastatic sarcoma cells.
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spelling pubmed-37354232013-08-07 Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling Kosla, Jan Paňková, Daniela Plachý, Jiří Tolde, Ondřej Bicanová, Kristýna Dvořák, Michal Rösel, Daniel Brábek, Jan Cell Commun Signal Research BACKGROUND: Although there is extensive evidence for the amoeboid invasiveness of cancer cells in vitro, much less is known about the role of amoeboid invasiveness in metastasis and the importance of Rho/ROCK/MLC signaling in this process. RESULTS: We analyzed the dependence of amoeboid invasiveness of rat and chicken sarcoma cells and the metastatic activity of chicken cells on individual elements of the Rho/ROCK/MLC pathway. In both animal models, inhibition of Rho, ROCK or MLC resulted in greatly decreased cell invasiveness in vitro, while inhibition of extracellular proteases using a broad spectrum inhibitor did not have a significant effect. The inhibition of both Rho activity and MLC phosphorylation by dominant negative mutants led to a decreased capability of chicken sarcoma cells to metastasize. Moreover, the overexpression of RhoA in non-metastatic chicken cells resulted in the rescue of both invasiveness and metastatic capability. Rho and ROCK, unlike MLC, appeared to be directly involved in the maintenance of the amoeboid phenotype, as their inhibition resulted in the amoeboid-mesenchymal transition in analyzed cell lines. CONCLUSION: Taken together, these results suggest that protease-independent invasion controlled by elements of the Rho/ROCK/MLC pathway can be frequently exploited by metastatic sarcoma cells. BioMed Central 2013-07-30 /pmc/articles/PMC3735423/ /pubmed/23899007 http://dx.doi.org/10.1186/1478-811X-11-51 Text en Copyright © 2013 Kosla et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Kosla, Jan
Paňková, Daniela
Plachý, Jiří
Tolde, Ondřej
Bicanová, Kristýna
Dvořák, Michal
Rösel, Daniel
Brábek, Jan
Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
title Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
title_full Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
title_fullStr Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
title_full_unstemmed Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
title_short Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
title_sort metastasis of aggressive amoeboid sarcoma cells is dependent on rho/rock/mlc signaling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735423/
https://www.ncbi.nlm.nih.gov/pubmed/23899007
http://dx.doi.org/10.1186/1478-811X-11-51
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