Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment

Detachment of cancer cells is the first step in tumor metastasis and malignancy. However, studies on the balance of initial tumor anchoring and detachment are limited. Herein, we revealed that the regulation of cytoskeleton proteins potentiates tumor detachment. The blockage of TGF-β1 using neutrali...

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Autores principales:	Jei-Ming Peng, Wei-Yu Chen, Jai-Hong Cheng, Jia-Wun Luo, Hong-Tai Tzeng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	invasive leading cells TGF-β1 actin cytoskeleton remodeling vimentin intermediate filament networks cell detachment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/355202647d7743a9885614105910abc5
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spelling	oai:doaj.org-article:355202647d7743a9885614105910abc52021-11-25T17:02:05ZDysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment10.3390/cancers132256482072-6694https://doaj.org/article/355202647d7743a9885614105910abc52021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5648https://doaj.org/toc/2072-6694Detachment of cancer cells is the first step in tumor metastasis and malignancy. However, studies on the balance of initial tumor anchoring and detachment are limited. Herein, we revealed that the regulation of cytoskeleton proteins potentiates tumor detachment. The blockage of TGF-β1 using neutralizing antibodies induced cancer cell detachment in the Boyden chamber and 3D in-gel spheroid models. Moreover, treatment with latrunculin B, an actin polymerization inhibitor, enhanced cell dissociation by abolishing actin fibers, indicating that TGF-β1 mediates the formation of actin stress fibers, and is likely responsible for the dynamics of anchoring and detachment. Indeed, latrunculin B disrupted the formation of external TGF-β1-induced actin fibers and translocation of intracellular vinculin, a focal adhesion protein, resulting in the suppression of cell adhesion. Moreover, the silencing of vimentin substantially reduced cell adhesion and enhanced cell detachment, revealing that cell adhesion and focal adhesion protein translocation stimulated by TGF-β1 require vimentin. Using the 3D in-gel spheroid model, we found that latrunculin B suppressed the cell adhesion promoted by external TGF-β1, increasing the number of cells that penetrated the Matrigel and detached from the tumor spheres. Thus, cytoskeleton remodeling maintained the balance of cell anchoring and detachment, and the TGF-β1/vimentin/focal adhesion protein assembly axis was involved in the control dynamics of initial tumor detachment.Jei-Ming PengWei-Yu ChenJai-Hong ChengJia-Wun LuoHong-Tai TzengMDPI AGarticleinvasive leading cellsTGF-β1actin cytoskeleton remodelingvimentin intermediate filament networkscell detachmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5648, p 5648 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	invasive leading cells TGF-β1 actin cytoskeleton remodeling vimentin intermediate filament networks cell detachment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	invasive leading cells TGF-β1 actin cytoskeleton remodeling vimentin intermediate filament networks cell detachment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jei-Ming Peng Wei-Yu Chen Jai-Hong Cheng Jia-Wun Luo Hong-Tai Tzeng Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment
description	Detachment of cancer cells is the first step in tumor metastasis and malignancy. However, studies on the balance of initial tumor anchoring and detachment are limited. Herein, we revealed that the regulation of cytoskeleton proteins potentiates tumor detachment. The blockage of TGF-β1 using neutralizing antibodies induced cancer cell detachment in the Boyden chamber and 3D in-gel spheroid models. Moreover, treatment with latrunculin B, an actin polymerization inhibitor, enhanced cell dissociation by abolishing actin fibers, indicating that TGF-β1 mediates the formation of actin stress fibers, and is likely responsible for the dynamics of anchoring and detachment. Indeed, latrunculin B disrupted the formation of external TGF-β1-induced actin fibers and translocation of intracellular vinculin, a focal adhesion protein, resulting in the suppression of cell adhesion. Moreover, the silencing of vimentin substantially reduced cell adhesion and enhanced cell detachment, revealing that cell adhesion and focal adhesion protein translocation stimulated by TGF-β1 require vimentin. Using the 3D in-gel spheroid model, we found that latrunculin B suppressed the cell adhesion promoted by external TGF-β1, increasing the number of cells that penetrated the Matrigel and detached from the tumor spheres. Thus, cytoskeleton remodeling maintained the balance of cell anchoring and detachment, and the TGF-β1/vimentin/focal adhesion protein assembly axis was involved in the control dynamics of initial tumor detachment.
format	article
author	Jei-Ming Peng Wei-Yu Chen Jai-Hong Cheng Jia-Wun Luo Hong-Tai Tzeng
author_facet	Jei-Ming Peng Wei-Yu Chen Jai-Hong Cheng Jia-Wun Luo Hong-Tai Tzeng
author_sort	Jei-Ming Peng
title	Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment
title_short	Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment
title_full	Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment
title_fullStr	Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment
title_full_unstemmed	Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment
title_sort	dysregulation of cytoskeleton remodeling drives invasive leading cells detachment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/355202647d7743a9885614105910abc5
work_keys_str_mv	AT jeimingpeng dysregulationofcytoskeletonremodelingdrivesinvasiveleadingcellsdetachment AT weiyuchen dysregulationofcytoskeletonremodelingdrivesinvasiveleadingcellsdetachment AT jaihongcheng dysregulationofcytoskeletonremodelingdrivesinvasiveleadingcellsdetachment AT jiawunluo dysregulationofcytoskeletonremodelingdrivesinvasiveleadingcellsdetachment AT hongtaitzeng dysregulationofcytoskeletonremodelingdrivesinvasiveleadingcellsdetachment
_version_	1718412769019035648

Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment

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