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ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells

Tumor aggressiveness is usually associated with metastasis. MDA-MB 231, a triple-negative breast cancer (TNBC), is an aggressive type of breast cancer and associated with early metastasis. The Rho/ROCK pathway is a key regulator of cell motility involving cytoskeleton regulation through stabilizatio...

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Autores principales: Guerra, Fabiana Sélos, Oliveira, Ramon Guerra de, Fraga, Carlos Alberto Manssour, Mermelstein, Claudia dos Santos, Fernandes, Patricia Dias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651822/
https://www.ncbi.nlm.nih.gov/pubmed/29057980
http://dx.doi.org/10.1038/s41598-017-14216-z
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author Guerra, Fabiana Sélos
Oliveira, Ramon Guerra de
Fraga, Carlos Alberto Manssour
Mermelstein, Claudia dos Santos
Fernandes, Patricia Dias
author_facet Guerra, Fabiana Sélos
Oliveira, Ramon Guerra de
Fraga, Carlos Alberto Manssour
Mermelstein, Claudia dos Santos
Fernandes, Patricia Dias
author_sort Guerra, Fabiana Sélos
collection PubMed
description Tumor aggressiveness is usually associated with metastasis. MDA-MB 231, a triple-negative breast cancer (TNBC), is an aggressive type of breast cancer and associated with early metastasis. The Rho/ROCK pathway is a key regulator of cell motility involving cytoskeleton regulation through stabilization of actin filaments and stress fiber formation. In this study we show that Fasudil, a ROCK inhibitor, inhibited the migration of MDA-MB 231 and A549 cells, without altering the viability of these cells at the concentration of 10 μM, modified tumor cell morphology, with disorganization of stress fibers and promotes activation of the canonical-Wnt/beta-catenin pathway. Therefore, Fasudil present a promising approach to the prevention of breast cancer metastasis through a different mechanism of action from the well-known one.
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spelling pubmed-56518222017-10-26 ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells Guerra, Fabiana Sélos Oliveira, Ramon Guerra de Fraga, Carlos Alberto Manssour Mermelstein, Claudia dos Santos Fernandes, Patricia Dias Sci Rep Article Tumor aggressiveness is usually associated with metastasis. MDA-MB 231, a triple-negative breast cancer (TNBC), is an aggressive type of breast cancer and associated with early metastasis. The Rho/ROCK pathway is a key regulator of cell motility involving cytoskeleton regulation through stabilization of actin filaments and stress fiber formation. In this study we show that Fasudil, a ROCK inhibitor, inhibited the migration of MDA-MB 231 and A549 cells, without altering the viability of these cells at the concentration of 10 μM, modified tumor cell morphology, with disorganization of stress fibers and promotes activation of the canonical-Wnt/beta-catenin pathway. Therefore, Fasudil present a promising approach to the prevention of breast cancer metastasis through a different mechanism of action from the well-known one. Nature Publishing Group UK 2017-10-20 /pmc/articles/PMC5651822/ /pubmed/29057980 http://dx.doi.org/10.1038/s41598-017-14216-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Guerra, Fabiana Sélos
Oliveira, Ramon Guerra de
Fraga, Carlos Alberto Manssour
Mermelstein, Claudia dos Santos
Fernandes, Patricia Dias
ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells
title ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells
title_full ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells
title_fullStr ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells
title_full_unstemmed ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells
title_short ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells
title_sort rock inhibition with fasudil induces beta-catenin nuclear translocation and inhibits cell migration of mda-mb 231 human breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651822/
https://www.ncbi.nlm.nih.gov/pubmed/29057980
http://dx.doi.org/10.1038/s41598-017-14216-z
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