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Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor of childhood. The heterogeneous microenvironment of solid tumors contains hypoxic regions associated with poor prognosis and chemoresistance. Hypoxia implicates the actin cytoskeleton through its essential roles in motility, invas...

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Autores principales: Glass, Joshua J., Phillips, Phoebe A., Gunning, Peter W., Stehn, Justine R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608101/
https://www.ncbi.nlm.nih.gov/pubmed/26475688
http://dx.doi.org/10.1186/s12885-015-1741-8
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author Glass, Joshua J.
Phillips, Phoebe A.
Gunning, Peter W.
Stehn, Justine R.
author_facet Glass, Joshua J.
Phillips, Phoebe A.
Gunning, Peter W.
Stehn, Justine R.
author_sort Glass, Joshua J.
collection PubMed
description BACKGROUND: Neuroblastoma is the most common extracranial solid tumor of childhood. The heterogeneous microenvironment of solid tumors contains hypoxic regions associated with poor prognosis and chemoresistance. Hypoxia implicates the actin cytoskeleton through its essential roles in motility, invasion and proliferation. However, hypoxia-induced changes in the actin cytoskeleton have only recently been observed in human cells. Tropomyosins are key regulators of the actin cytoskeleton and we hypothesized that tropomyosins may mediate hypoxic phenotypes. METHODS: Neuroblastoma (SH-EP) cells were incubated ± hypoxia (1 % O(2), 5 % CO(2)) for up to 144 h, before examining the cytoskeleton by confocal microscopy and Western blotting. RESULTS: Hypoxic cells were characterized by a more organized actin cytoskeleton and a reduced ability to degrade gelatin substrates. Hypoxia significantly increased mean actin filament bundle width (72 h) and actin filament length (72–96 h). This correlated with increased hypoxic expression and filamentous organization of stabilizing tropomyosins Tm1 and Tm2. However, isoform specific changes in tropomyosin expression were more evident at 96 h. CONCLUSIONS: This study demonstrates hypoxia-induced changes in the recruitment of high molecular weight tropomyosins into the actin stress fibres of a human cancer. While hypoxia induced clear changes in actin organization compared with parallel normoxic cultures of neuroblastoma, the precise role of tropomyosins in this hypoxic actin reorganization remains to be determined. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1741-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-46081012015-10-17 Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells Glass, Joshua J. Phillips, Phoebe A. Gunning, Peter W. Stehn, Justine R. BMC Cancer Research Article BACKGROUND: Neuroblastoma is the most common extracranial solid tumor of childhood. The heterogeneous microenvironment of solid tumors contains hypoxic regions associated with poor prognosis and chemoresistance. Hypoxia implicates the actin cytoskeleton through its essential roles in motility, invasion and proliferation. However, hypoxia-induced changes in the actin cytoskeleton have only recently been observed in human cells. Tropomyosins are key regulators of the actin cytoskeleton and we hypothesized that tropomyosins may mediate hypoxic phenotypes. METHODS: Neuroblastoma (SH-EP) cells were incubated ± hypoxia (1 % O(2), 5 % CO(2)) for up to 144 h, before examining the cytoskeleton by confocal microscopy and Western blotting. RESULTS: Hypoxic cells were characterized by a more organized actin cytoskeleton and a reduced ability to degrade gelatin substrates. Hypoxia significantly increased mean actin filament bundle width (72 h) and actin filament length (72–96 h). This correlated with increased hypoxic expression and filamentous organization of stabilizing tropomyosins Tm1 and Tm2. However, isoform specific changes in tropomyosin expression were more evident at 96 h. CONCLUSIONS: This study demonstrates hypoxia-induced changes in the recruitment of high molecular weight tropomyosins into the actin stress fibres of a human cancer. While hypoxia induced clear changes in actin organization compared with parallel normoxic cultures of neuroblastoma, the precise role of tropomyosins in this hypoxic actin reorganization remains to be determined. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1741-8) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-16 /pmc/articles/PMC4608101/ /pubmed/26475688 http://dx.doi.org/10.1186/s12885-015-1741-8 Text en © Glass et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Glass, Joshua J.
Phillips, Phoebe A.
Gunning, Peter W.
Stehn, Justine R.
Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells
title Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells
title_full Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells
title_fullStr Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells
title_full_unstemmed Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells
title_short Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells
title_sort hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608101/
https://www.ncbi.nlm.nih.gov/pubmed/26475688
http://dx.doi.org/10.1186/s12885-015-1741-8
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