Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells

Actomyosin contractility regulates various cellular processes including proliferation and differentiation while dysregulation of actomyosin activity contributes to cancer development and progression. Previously, we have reported that actomyosin-generated tension at adherens junctions is required for...

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Autores principales: Oleg Dobrokhotov, Masaki Sunagawa, Takeru Torii, Shinji Mii, Keiko Kawauchi, Atsushi Enomoto, Masahiro Sokabe, Hiroaki Hirata
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:e5a1bf86e04c4c7e80dd0a75ec3d52342021-11-11T08:04:10ZAnti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells2296-634X10.3389/fcell.2021.728383https://doaj.org/article/e5a1bf86e04c4c7e80dd0a75ec3d52342021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.728383/fullhttps://doaj.org/toc/2296-634XActomyosin contractility regulates various cellular processes including proliferation and differentiation while dysregulation of actomyosin activity contributes to cancer development and progression. Previously, we have reported that actomyosin-generated tension at adherens junctions is required for cell density-dependent inhibition of proliferation of normal skin keratinocytes. However, it remains unclear how actomyosin contractility affects the hyperproliferation ability of cutaneous squamous cell carcinoma (cSCC) cells. In this study, we find that actomyosin activity is impaired in cSCC cells both in vitro and in vivo. External application of tensile loads to adherens junctions by sustained mechanical stretch attenuates the proliferation of cSCC cells, which depends on intact adherens junctions. Forced activation of actomyosin of cSCC cells also inhibits their proliferation in a cell-cell contact-dependent manner. Furthermore, the cell cycle arrest induced by tensile loading to adherens junctions is accompanied by epidermal differentiation in cSCC cells. Our results show that the degree of malignant properties of cSCC cells can be reduced by applying tensile loads to adherens junctions, which implies that the mechanical status of adherens junctions may serve as a novel therapeutic target for cSCC.Oleg DobrokhotovMasaki SunagawaMasaki SunagawaTakeru ToriiShinji MiiKeiko KawauchiAtsushi EnomotoMasahiro SokabeHiroaki HirataFrontiers Media S.A.articleactomyosinadherens junctioncontact inhibitionmechanosensingmechanotransductionepidermoid carcinomaBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution DOAJ
collection DOAJ
language EN
topic actomyosin
adherens junction
contact inhibition
mechanosensing
mechanotransduction
epidermoid carcinoma
Biology (General)
QH301-705.5
spellingShingle actomyosin
adherens junction
contact inhibition
mechanosensing
mechanotransduction
epidermoid carcinoma
Biology (General)
QH301-705.5
Oleg Dobrokhotov
Masaki Sunagawa
Masaki Sunagawa
Takeru Torii
Shinji Mii
Keiko Kawauchi
Atsushi Enomoto
Masahiro Sokabe
Hiroaki Hirata
Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells
description Actomyosin contractility regulates various cellular processes including proliferation and differentiation while dysregulation of actomyosin activity contributes to cancer development and progression. Previously, we have reported that actomyosin-generated tension at adherens junctions is required for cell density-dependent inhibition of proliferation of normal skin keratinocytes. However, it remains unclear how actomyosin contractility affects the hyperproliferation ability of cutaneous squamous cell carcinoma (cSCC) cells. In this study, we find that actomyosin activity is impaired in cSCC cells both in vitro and in vivo. External application of tensile loads to adherens junctions by sustained mechanical stretch attenuates the proliferation of cSCC cells, which depends on intact adherens junctions. Forced activation of actomyosin of cSCC cells also inhibits their proliferation in a cell-cell contact-dependent manner. Furthermore, the cell cycle arrest induced by tensile loading to adherens junctions is accompanied by epidermal differentiation in cSCC cells. Our results show that the degree of malignant properties of cSCC cells can be reduced by applying tensile loads to adherens junctions, which implies that the mechanical status of adherens junctions may serve as a novel therapeutic target for cSCC.
format article
author Oleg Dobrokhotov
Masaki Sunagawa
Masaki Sunagawa
Takeru Torii
Shinji Mii
Keiko Kawauchi
Atsushi Enomoto
Masahiro Sokabe
Hiroaki Hirata
author_facet Oleg Dobrokhotov
Masaki Sunagawa
Masaki Sunagawa
Takeru Torii
Shinji Mii
Keiko Kawauchi
Atsushi Enomoto
Masahiro Sokabe
Hiroaki Hirata
author_sort Oleg Dobrokhotov
title Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells
title_short Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells
title_full Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells
title_fullStr Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells
title_full_unstemmed Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells
title_sort anti-malignant effect of tensile loading to adherens junctions in cutaneous squamous cell carcinoma cells
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/e5a1bf86e04c4c7e80dd0a75ec3d5234
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