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αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion

The malignant brain cancer glioblastoma multiforme (GBM) displays invasive growth behaviors that are regulated by extracellular cues within the neural microenvironment. The adhesion and signaling pathways that drive GBM cell invasion remain largely uncharacterized. Here we use human GBM cell lines,...

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Autores principales: Reyes, Steve B., Narayanan, Anjana S., Lee, Hye Shin, Tchaicha, Jeremy H., Aldape, Kenneth D., Lang, Frederick F., Tolias, Kimberly F., McCarty, Joseph H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571870/
https://www.ncbi.nlm.nih.gov/pubmed/23283986
http://dx.doi.org/10.1091/mbc.E12-07-0521
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author Reyes, Steve B.
Narayanan, Anjana S.
Lee, Hye Shin
Tchaicha, Jeremy H.
Aldape, Kenneth D.
Lang, Frederick F.
Tolias, Kimberly F.
McCarty, Joseph H.
author_facet Reyes, Steve B.
Narayanan, Anjana S.
Lee, Hye Shin
Tchaicha, Jeremy H.
Aldape, Kenneth D.
Lang, Frederick F.
Tolias, Kimberly F.
McCarty, Joseph H.
author_sort Reyes, Steve B.
collection PubMed
description The malignant brain cancer glioblastoma multiforme (GBM) displays invasive growth behaviors that are regulated by extracellular cues within the neural microenvironment. The adhesion and signaling pathways that drive GBM cell invasion remain largely uncharacterized. Here we use human GBM cell lines, primary patient samples, and preclinical mouse models to demonstrate that integrin αvβ8 is a major driver of GBM cell invasion. β8 integrin is overexpressed in many human GBM cells, with higher integrin expression correlating with increased invasion and diminished patient survival. Silencing β8 integrin in human GBM cells leads to impaired tumor cell invasion due to hyperactivation of the Rho GTPases Rac1 and Cdc42. β8 integrin coimmunoprecipitates with Rho-GDP dissociation inhibitor 1 (RhoGDI1), an intracellular signaling effector that sequesters Rho GTPases in their inactive GDP-bound states. Silencing RhoGDI1 expression or uncoupling αvβ8 integrin–RhoGDI1 protein interactions blocks GBM cell invasion due to Rho GTPase hyperactivation. These data reveal for the first time that αvβ8 integrin, via interactions with RhoGDI1, regulates activation of Rho proteins to promote GBM cell invasiveness. Hence targeting the αvβ8 integrin–RhoGDI1 signaling axis might be an effective strategy for blocking GBM cell invasion.
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spelling pubmed-35718702013-04-30 αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion Reyes, Steve B. Narayanan, Anjana S. Lee, Hye Shin Tchaicha, Jeremy H. Aldape, Kenneth D. Lang, Frederick F. Tolias, Kimberly F. McCarty, Joseph H. Mol Biol Cell Articles The malignant brain cancer glioblastoma multiforme (GBM) displays invasive growth behaviors that are regulated by extracellular cues within the neural microenvironment. The adhesion and signaling pathways that drive GBM cell invasion remain largely uncharacterized. Here we use human GBM cell lines, primary patient samples, and preclinical mouse models to demonstrate that integrin αvβ8 is a major driver of GBM cell invasion. β8 integrin is overexpressed in many human GBM cells, with higher integrin expression correlating with increased invasion and diminished patient survival. Silencing β8 integrin in human GBM cells leads to impaired tumor cell invasion due to hyperactivation of the Rho GTPases Rac1 and Cdc42. β8 integrin coimmunoprecipitates with Rho-GDP dissociation inhibitor 1 (RhoGDI1), an intracellular signaling effector that sequesters Rho GTPases in their inactive GDP-bound states. Silencing RhoGDI1 expression or uncoupling αvβ8 integrin–RhoGDI1 protein interactions blocks GBM cell invasion due to Rho GTPase hyperactivation. These data reveal for the first time that αvβ8 integrin, via interactions with RhoGDI1, regulates activation of Rho proteins to promote GBM cell invasiveness. Hence targeting the αvβ8 integrin–RhoGDI1 signaling axis might be an effective strategy for blocking GBM cell invasion. The American Society for Cell Biology 2013-02-15 /pmc/articles/PMC3571870/ /pubmed/23283986 http://dx.doi.org/10.1091/mbc.E12-07-0521 Text en © 2013 Reyes 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
Reyes, Steve B.
Narayanan, Anjana S.
Lee, Hye Shin
Tchaicha, Jeremy H.
Aldape, Kenneth D.
Lang, Frederick F.
Tolias, Kimberly F.
McCarty, Joseph H.
αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion
title αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion
title_full αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion
title_fullStr αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion
title_full_unstemmed αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion
title_short αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion
title_sort αvβ8 integrin interacts with rhogdi1 to regulate rac1 and cdc42 activation and drive glioblastoma cell invasion
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571870/
https://www.ncbi.nlm.nih.gov/pubmed/23283986
http://dx.doi.org/10.1091/mbc.E12-07-0521
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