Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.

Heregulin (HRG) β1 signaling promotes scattering of MCF7 cells by inducing breakdown of adherens and tight junctions. Here, we show that stimulation with HRG-β1 causes the F-actin backbone of junctions to destabilize prior to the loss of adherent proteins and scattering of the cells. The adherent pr...

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Main Authors: Rintaro Okoshi, Chung-Li Shu, Sayoko Ihara, Yasuhisa Fukui
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3538754?pdf=render
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author Rintaro Okoshi
Chung-Li Shu
Sayoko Ihara
Yasuhisa Fukui
author_facet Rintaro Okoshi
Chung-Li Shu
Sayoko Ihara
Yasuhisa Fukui
author_sort Rintaro Okoshi
collection DOAJ
description Heregulin (HRG) β1 signaling promotes scattering of MCF7 cells by inducing breakdown of adherens and tight junctions. Here, we show that stimulation with HRG-β1 causes the F-actin backbone of junctions to destabilize prior to the loss of adherent proteins and scattering of the cells. The adherent proteins dissociate and translocate from cell-cell junctions to the cytosol. Moreover, using inhibitors we show that the MEK1 pathway is required for the disappearance of F-actin from junctions and p38 MAP kinase activity is essential for scattering of the cells. Upon treatment with a p38 MAP kinase inhibitor, adherens junction complexes immediately reassemble, most likely in the cytoplasm, and move to the plasma membrane in cells dissociated by HRG-β1 stimulation. Subsequently, tight junction complexes form, most likely in the cytoplasm, and move to the plasma membrane. Thus, the p38 MAP kinase inhibitor causes a re-aggregation of scattered cells, even in the presence of HRG-β1. These results suggest that p38 MAP kinase signaling to adherens junction proteins regulates cell aggregation, providing a novel understanding of the regulation of cell-cell adhesion.
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spelling doaj.art-040ef11b836d45b9b239f7c9853a70f92022-12-21T20:31:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5329810.1371/journal.pone.0053298Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.Rintaro OkoshiChung-Li ShuSayoko IharaYasuhisa FukuiHeregulin (HRG) β1 signaling promotes scattering of MCF7 cells by inducing breakdown of adherens and tight junctions. Here, we show that stimulation with HRG-β1 causes the F-actin backbone of junctions to destabilize prior to the loss of adherent proteins and scattering of the cells. The adherent proteins dissociate and translocate from cell-cell junctions to the cytosol. Moreover, using inhibitors we show that the MEK1 pathway is required for the disappearance of F-actin from junctions and p38 MAP kinase activity is essential for scattering of the cells. Upon treatment with a p38 MAP kinase inhibitor, adherens junction complexes immediately reassemble, most likely in the cytoplasm, and move to the plasma membrane in cells dissociated by HRG-β1 stimulation. Subsequently, tight junction complexes form, most likely in the cytoplasm, and move to the plasma membrane. Thus, the p38 MAP kinase inhibitor causes a re-aggregation of scattered cells, even in the presence of HRG-β1. These results suggest that p38 MAP kinase signaling to adherens junction proteins regulates cell aggregation, providing a novel understanding of the regulation of cell-cell adhesion.http://europepmc.org/articles/PMC3538754?pdf=render
spellingShingle Rintaro Okoshi
Chung-Li Shu
Sayoko Ihara
Yasuhisa Fukui
Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.
PLoS ONE
title Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.
title_full Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.
title_fullStr Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.
title_full_unstemmed Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.
title_short Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.
title_sort scattering of mcf7 cells by heregulin ss 1 depends on the mek and p38 map kinase pathway
url http://europepmc.org/articles/PMC3538754?pdf=render
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AT sayokoihara scatteringofmcf7cellsbyheregulinß1dependsonthemekandp38mapkinasepathway
AT yasuhisafukui scatteringofmcf7cellsbyheregulinß1dependsonthemekandp38mapkinasepathway