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Y‐27632, an Inhibitor of Rho‐associated Protein Kinase, Suppresses Tumor Cell Invasion via Regulation of Focal Adhesion and Focal Adhesion Kinase

Migration of rat ascites hepatoma (MM1) cells, invasion and phagokinetic movement were induced by the combination of lysophosphatidic acid (LPA) and fibronectin (FN). Induction of migratory activity was tightly correlated with morphological change of MM1 cells from spherical or polygonal‐shaped cell...

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Autores principales: Imamura, Fumio, Mukai, Mutsuko, Ayaki, Masako, Akedo, and Hitoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926426/
https://www.ncbi.nlm.nih.gov/pubmed/10965022
http://dx.doi.org/10.1111/j.1349-7006.2000.tb01018.x
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author Imamura, Fumio
Mukai, Mutsuko
Ayaki, Masako
Akedo, and Hitoshi
author_facet Imamura, Fumio
Mukai, Mutsuko
Ayaki, Masako
Akedo, and Hitoshi
author_sort Imamura, Fumio
collection PubMed
description Migration of rat ascites hepatoma (MM1) cells, invasion and phagokinetic movement were induced by the combination of lysophosphatidic acid (LPA) and fibronectin (FN). Induction of migratory activity was tightly correlated with morphological change of MM1 cells from spherical or polygonal‐shaped cells to fusiform‐shaped ones with pseudopodia. MM1 cells were mobile in a fusiform shape, whereas those of a spherical or polygonal shape were not. A small GTPase Rho and one of its downstream effectors ROCK (Rho‐associated coiled‐coil forming protein kinase), play essential roles in these processes, as evidenced by suppression of migration and morphological change of MM1 cells by Clostridium botulinum C3 exoenzyme, an inhibitor of Rho, or by Y‐27632, an inhibitor of ROCK. Y‐27632 also suppressed the formation of fusiform‐shaped pseudopodia‐carrying MM1 cells that was induced by stimulation with the combination of LPA and FN. LPA and FN also evoked the formation of focal adhesions and actin bundles, and tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin. The inhibitory effect of Y‐27632 on LPA‐induced migration and morphological change of MM1 cells was considered to be mediated, at least in part, by impaired formation of focal adhesions and actin bundles. Y‐27632 suppressed LPA‐induced tyrosine phosphorylation of FAK and paxillin, suggesting that ROCK regulates these molecules and Y‐27632 inhibits cellular migration and morphological change, at least in part, through this regulation.
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spelling pubmed-59264262018-05-11 Y‐27632, an Inhibitor of Rho‐associated Protein Kinase, Suppresses Tumor Cell Invasion via Regulation of Focal Adhesion and Focal Adhesion Kinase Imamura, Fumio Mukai, Mutsuko Ayaki, Masako Akedo, and Hitoshi Jpn J Cancer Res Article Migration of rat ascites hepatoma (MM1) cells, invasion and phagokinetic movement were induced by the combination of lysophosphatidic acid (LPA) and fibronectin (FN). Induction of migratory activity was tightly correlated with morphological change of MM1 cells from spherical or polygonal‐shaped cells to fusiform‐shaped ones with pseudopodia. MM1 cells were mobile in a fusiform shape, whereas those of a spherical or polygonal shape were not. A small GTPase Rho and one of its downstream effectors ROCK (Rho‐associated coiled‐coil forming protein kinase), play essential roles in these processes, as evidenced by suppression of migration and morphological change of MM1 cells by Clostridium botulinum C3 exoenzyme, an inhibitor of Rho, or by Y‐27632, an inhibitor of ROCK. Y‐27632 also suppressed the formation of fusiform‐shaped pseudopodia‐carrying MM1 cells that was induced by stimulation with the combination of LPA and FN. LPA and FN also evoked the formation of focal adhesions and actin bundles, and tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin. The inhibitory effect of Y‐27632 on LPA‐induced migration and morphological change of MM1 cells was considered to be mediated, at least in part, by impaired formation of focal adhesions and actin bundles. Y‐27632 suppressed LPA‐induced tyrosine phosphorylation of FAK and paxillin, suggesting that ROCK regulates these molecules and Y‐27632 inhibits cellular migration and morphological change, at least in part, through this regulation. Blackwell Publishing Ltd 2000-08 /pmc/articles/PMC5926426/ /pubmed/10965022 http://dx.doi.org/10.1111/j.1349-7006.2000.tb01018.x Text en
spellingShingle Article
Imamura, Fumio
Mukai, Mutsuko
Ayaki, Masako
Akedo, and Hitoshi
Y‐27632, an Inhibitor of Rho‐associated Protein Kinase, Suppresses Tumor Cell Invasion via Regulation of Focal Adhesion and Focal Adhesion Kinase
title Y‐27632, an Inhibitor of Rho‐associated Protein Kinase, Suppresses Tumor Cell Invasion via Regulation of Focal Adhesion and Focal Adhesion Kinase
title_full Y‐27632, an Inhibitor of Rho‐associated Protein Kinase, Suppresses Tumor Cell Invasion via Regulation of Focal Adhesion and Focal Adhesion Kinase
title_fullStr Y‐27632, an Inhibitor of Rho‐associated Protein Kinase, Suppresses Tumor Cell Invasion via Regulation of Focal Adhesion and Focal Adhesion Kinase
title_full_unstemmed Y‐27632, an Inhibitor of Rho‐associated Protein Kinase, Suppresses Tumor Cell Invasion via Regulation of Focal Adhesion and Focal Adhesion Kinase
title_short Y‐27632, an Inhibitor of Rho‐associated Protein Kinase, Suppresses Tumor Cell Invasion via Regulation of Focal Adhesion and Focal Adhesion Kinase
title_sort y‐27632, an inhibitor of rho‐associated protein kinase, suppresses tumor cell invasion via regulation of focal adhesion and focal adhesion kinase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926426/
https://www.ncbi.nlm.nih.gov/pubmed/10965022
http://dx.doi.org/10.1111/j.1349-7006.2000.tb01018.x
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