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Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion and experimental metastasis

Rho GTPases control cytoskeletal dynamics through cytoplasmic effectors, and regulate transcriptional activation by the Myocardin Related Transcription Factors (MRTFs), coactivators for Serum Response Factor (SRF). We used RNAi to investigate the contribution of the MRTF-SRF pathway to cytoskeletal...

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Autores principales: Medjkane, Souhila, Perez-Sanchez, Cristina, Gaggioli, Cedric, Sahai, Erik, Treisman, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089348/
https://www.ncbi.nlm.nih.gov/pubmed/19198601
http://dx.doi.org/10.1038/ncb1833
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author Medjkane, Souhila
Perez-Sanchez, Cristina
Gaggioli, Cedric
Sahai, Erik
Treisman, Richard
author_facet Medjkane, Souhila
Perez-Sanchez, Cristina
Gaggioli, Cedric
Sahai, Erik
Treisman, Richard
author_sort Medjkane, Souhila
collection PubMed
description Rho GTPases control cytoskeletal dynamics through cytoplasmic effectors, and regulate transcriptional activation by the Myocardin Related Transcription Factors (MRTFs), coactivators for Serum Response Factor (SRF). We used RNAi to investigate the contribution of the MRTF-SRF pathway to cytoskeletal dynamics in MDA-MB-231 breast carcinoma and B16F2 melanoma cells, where basal MRTF-SRF activity is Rho-dependent. Depletion of MRTFs or SRF reduces cell adhesion, spreading, invasion and motility in culture, without affecting proliferation or inducing apoptosis; MRTF-depleted tumor cell xenografts exhibit reduced cell motility but proliferate normally. MRTF- and SRF-depleted tumor cells fail to colonise the lung from the bloodstream, being unable to persist following their initial arrival at the lung. Only a few genes exhibit MRTF-dependent expression in both cell lines. Two of these, MYH9 (MLC2) and MYL9 (NMHCIIa), are also required for invasion and lung colonisation. Conversely, expression of an activated MRTF increases lung colonisation by poorly metastatic B16F0 cells. Actin-based cell behaviour and experimental metastasis thus requires Rho-dependent nuclear signalling through the MRTF-SRF network.
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spelling pubmed-60893482018-08-13 Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion and experimental metastasis Medjkane, Souhila Perez-Sanchez, Cristina Gaggioli, Cedric Sahai, Erik Treisman, Richard Nat Cell Biol Article Rho GTPases control cytoskeletal dynamics through cytoplasmic effectors, and regulate transcriptional activation by the Myocardin Related Transcription Factors (MRTFs), coactivators for Serum Response Factor (SRF). We used RNAi to investigate the contribution of the MRTF-SRF pathway to cytoskeletal dynamics in MDA-MB-231 breast carcinoma and B16F2 melanoma cells, where basal MRTF-SRF activity is Rho-dependent. Depletion of MRTFs or SRF reduces cell adhesion, spreading, invasion and motility in culture, without affecting proliferation or inducing apoptosis; MRTF-depleted tumor cell xenografts exhibit reduced cell motility but proliferate normally. MRTF- and SRF-depleted tumor cells fail to colonise the lung from the bloodstream, being unable to persist following their initial arrival at the lung. Only a few genes exhibit MRTF-dependent expression in both cell lines. Two of these, MYH9 (MLC2) and MYL9 (NMHCIIa), are also required for invasion and lung colonisation. Conversely, expression of an activated MRTF increases lung colonisation by poorly metastatic B16F0 cells. Actin-based cell behaviour and experimental metastasis thus requires Rho-dependent nuclear signalling through the MRTF-SRF network. 2009-02-08 2009-03 /pmc/articles/PMC6089348/ /pubmed/19198601 http://dx.doi.org/10.1038/ncb1833 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Medjkane, Souhila
Perez-Sanchez, Cristina
Gaggioli, Cedric
Sahai, Erik
Treisman, Richard
Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion and experimental metastasis
title Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion and experimental metastasis
title_full Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion and experimental metastasis
title_fullStr Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion and experimental metastasis
title_full_unstemmed Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion and experimental metastasis
title_short Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion and experimental metastasis
title_sort myocardin-related transcription factors and srf are required for cytoskeletal dynamics, invasion and experimental metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089348/
https://www.ncbi.nlm.nih.gov/pubmed/19198601
http://dx.doi.org/10.1038/ncb1833
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