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Mechanical confinement triggers glioma linear migration dependent on formin FHOD3

Glioblastomas are extremely aggressive brain tumors with highly invasive properties. Brain linear tracks such as blood vessel walls constitute their main invasive routes. Here we analyze rat C6 and patient-derived glioma cell motility in vitro using micropatterned linear tracks to mimic blood vessel...

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Autores principales: Monzo, Pascale, Chong, Yuk Kien, Guetta-Terrier, Charlotte, Krishnasamy, Anitha, Sathe, Sharvari R., Yim, Evelyn K. F., Ng, Wai Hoe, Ang, Beng Ti, Tang, Carol, Ladoux, Benoit, Gauthier, Nils C., Sheetz, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831879/
https://www.ncbi.nlm.nih.gov/pubmed/26912794
http://dx.doi.org/10.1091/mbc.E15-08-0565
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author Monzo, Pascale
Chong, Yuk Kien
Guetta-Terrier, Charlotte
Krishnasamy, Anitha
Sathe, Sharvari R.
Yim, Evelyn K. F.
Ng, Wai Hoe
Ang, Beng Ti
Tang, Carol
Ladoux, Benoit
Gauthier, Nils C.
Sheetz, Michael P.
author_facet Monzo, Pascale
Chong, Yuk Kien
Guetta-Terrier, Charlotte
Krishnasamy, Anitha
Sathe, Sharvari R.
Yim, Evelyn K. F.
Ng, Wai Hoe
Ang, Beng Ti
Tang, Carol
Ladoux, Benoit
Gauthier, Nils C.
Sheetz, Michael P.
author_sort Monzo, Pascale
collection PubMed
description Glioblastomas are extremely aggressive brain tumors with highly invasive properties. Brain linear tracks such as blood vessel walls constitute their main invasive routes. Here we analyze rat C6 and patient-derived glioma cell motility in vitro using micropatterned linear tracks to mimic blood vessels. On laminin-coated tracks (3–10 μm), these cells used an efficient saltatory mode of migration similar to their in vivo migration. This saltatory migration was also observed on larger tracks (50–400 μm in width) at high cell densities. In these cases, the mechanical constraints imposed by neighboring cells triggered this efficient mode of migration, resulting in the formation of remarkable antiparallel streams of cells along the tracks. This motility involved microtubule-dependent polarization, contractile actin bundles and dynamic paxillin-containing adhesions in the leading process and in the tail. Glioma linear migration was dramatically reduced by inhibiting formins but, surprisingly, accelerated by inhibiting Arp2/3. Protein expression and phenotypic analysis indicated that the formin FHOD3 played a role in this motility but not mDia1 or mDia2. We propose that glioma migration under confinement on laminin relies on formins, including FHOD3, but not Arp2/3 and that the low level of adhesion allows rapid antiparallel migration.
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spelling pubmed-48318792016-06-30 Mechanical confinement triggers glioma linear migration dependent on formin FHOD3 Monzo, Pascale Chong, Yuk Kien Guetta-Terrier, Charlotte Krishnasamy, Anitha Sathe, Sharvari R. Yim, Evelyn K. F. Ng, Wai Hoe Ang, Beng Ti Tang, Carol Ladoux, Benoit Gauthier, Nils C. Sheetz, Michael P. Mol Biol Cell Articles Glioblastomas are extremely aggressive brain tumors with highly invasive properties. Brain linear tracks such as blood vessel walls constitute their main invasive routes. Here we analyze rat C6 and patient-derived glioma cell motility in vitro using micropatterned linear tracks to mimic blood vessels. On laminin-coated tracks (3–10 μm), these cells used an efficient saltatory mode of migration similar to their in vivo migration. This saltatory migration was also observed on larger tracks (50–400 μm in width) at high cell densities. In these cases, the mechanical constraints imposed by neighboring cells triggered this efficient mode of migration, resulting in the formation of remarkable antiparallel streams of cells along the tracks. This motility involved microtubule-dependent polarization, contractile actin bundles and dynamic paxillin-containing adhesions in the leading process and in the tail. Glioma linear migration was dramatically reduced by inhibiting formins but, surprisingly, accelerated by inhibiting Arp2/3. Protein expression and phenotypic analysis indicated that the formin FHOD3 played a role in this motility but not mDia1 or mDia2. We propose that glioma migration under confinement on laminin relies on formins, including FHOD3, but not Arp2/3 and that the low level of adhesion allows rapid antiparallel migration. The American Society for Cell Biology 2016-04-15 /pmc/articles/PMC4831879/ /pubmed/26912794 http://dx.doi.org/10.1091/mbc.E15-08-0565 Text en © 2016 Monzo 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 for Cell Biology.
spellingShingle Articles
Monzo, Pascale
Chong, Yuk Kien
Guetta-Terrier, Charlotte
Krishnasamy, Anitha
Sathe, Sharvari R.
Yim, Evelyn K. F.
Ng, Wai Hoe
Ang, Beng Ti
Tang, Carol
Ladoux, Benoit
Gauthier, Nils C.
Sheetz, Michael P.
Mechanical confinement triggers glioma linear migration dependent on formin FHOD3
title Mechanical confinement triggers glioma linear migration dependent on formin FHOD3
title_full Mechanical confinement triggers glioma linear migration dependent on formin FHOD3
title_fullStr Mechanical confinement triggers glioma linear migration dependent on formin FHOD3
title_full_unstemmed Mechanical confinement triggers glioma linear migration dependent on formin FHOD3
title_short Mechanical confinement triggers glioma linear migration dependent on formin FHOD3
title_sort mechanical confinement triggers glioma linear migration dependent on formin fhod3
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831879/
https://www.ncbi.nlm.nih.gov/pubmed/26912794
http://dx.doi.org/10.1091/mbc.E15-08-0565
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