The Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 2

We have investigated motility in breast cancer cell lines in association with the expression of Transglutaminase type 2 (TG2) as well as upon the administration of Doxorubicin (Dox), an active cytotoxic agent that is employed in chemotherapy. The exposure of MCF-7 cells to the drug increased TG2 lev...

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Autores principales:	Nicoletta Bianchi, Federica Brugnoli, Silvia Grassilli, Karine Bourgeois, Jeffrey W. Keillor, Carlo M. Bergamini, Gianluca Aguiari, Stefano Volinia, Valeria Bertagnolo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	transglutaminase type 2 breast cancer motility EMT NC9 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9f59f9c691c54a2d982335963878db74
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spelling	oai:doaj.org-article:9f59f9c691c54a2d982335963878db742021-11-25T17:10:58ZThe Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 210.3390/cells101130592073-4409https://doaj.org/article/9f59f9c691c54a2d982335963878db742021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3059https://doaj.org/toc/2073-4409We have investigated motility in breast cancer cell lines in association with the expression of Transglutaminase type 2 (TG2) as well as upon the administration of Doxorubicin (Dox), an active cytotoxic agent that is employed in chemotherapy. The exposure of MCF-7 cells to the drug increased TG2 levels, triggering epithelial–mesenchymal transition (EMT), thereby supporting cell motility. The effects of Dox on the movement of MCF-7 cells were counteracted by treatment with NC9, a TG2 inhibitor, which induced morphological changes and also reduced the migration of MDA-MB-231 cells exhibiting high levels of TG2. The physical association of TG2 with the cytoskeletal component vimentin appeared pivotal both in drug-treated MCF-7 and in MDA-MB-231 cells and seemed to be independent of the catalytic activity of TG2. NC9 altered the subcellular distribution of TG2 and, consequently, the co-localization of TG2 with vimentin. Furthermore, NC9 induced a nuclear accumulation of TG2 as a prelude to TG2-dependent gene expression modifications. Since enzyme activity can affect both motility and nuclear functions, targeting of this protein could represent a method to improve therapeutic interventions in breast tumors, particularly those to control progression and to limit drug resistance.Nicoletta BianchiFederica BrugnoliSilvia GrassilliKarine BourgeoisJeffrey W. KeillorCarlo M. BergaminiGianluca AguiariStefano VoliniaValeria BertagnoloMDPI AGarticletransglutaminase type 2breast cancermotilityEMTNC9Biology (General)QH301-705.5ENCells, Vol 10, Iss 3059, p 3059 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transglutaminase type 2 breast cancer motility EMT NC9 Biology (General) QH301-705.5
spellingShingle	transglutaminase type 2 breast cancer motility EMT NC9 Biology (General) QH301-705.5 Nicoletta Bianchi Federica Brugnoli Silvia Grassilli Karine Bourgeois Jeffrey W. Keillor Carlo M. Bergamini Gianluca Aguiari Stefano Volinia Valeria Bertagnolo The Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 2
description	We have investigated motility in breast cancer cell lines in association with the expression of Transglutaminase type 2 (TG2) as well as upon the administration of Doxorubicin (Dox), an active cytotoxic agent that is employed in chemotherapy. The exposure of MCF-7 cells to the drug increased TG2 levels, triggering epithelial–mesenchymal transition (EMT), thereby supporting cell motility. The effects of Dox on the movement of MCF-7 cells were counteracted by treatment with NC9, a TG2 inhibitor, which induced morphological changes and also reduced the migration of MDA-MB-231 cells exhibiting high levels of TG2. The physical association of TG2 with the cytoskeletal component vimentin appeared pivotal both in drug-treated MCF-7 and in MDA-MB-231 cells and seemed to be independent of the catalytic activity of TG2. NC9 altered the subcellular distribution of TG2 and, consequently, the co-localization of TG2 with vimentin. Furthermore, NC9 induced a nuclear accumulation of TG2 as a prelude to TG2-dependent gene expression modifications. Since enzyme activity can affect both motility and nuclear functions, targeting of this protein could represent a method to improve therapeutic interventions in breast tumors, particularly those to control progression and to limit drug resistance.
format	article
author	Nicoletta Bianchi Federica Brugnoli Silvia Grassilli Karine Bourgeois Jeffrey W. Keillor Carlo M. Bergamini Gianluca Aguiari Stefano Volinia Valeria Bertagnolo
author_facet	Nicoletta Bianchi Federica Brugnoli Silvia Grassilli Karine Bourgeois Jeffrey W. Keillor Carlo M. Bergamini Gianluca Aguiari Stefano Volinia Valeria Bertagnolo
author_sort	Nicoletta Bianchi
title	The Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 2
title_short	The Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 2
title_full	The Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 2
title_fullStr	The Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 2
title_full_unstemmed	The Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 2
title_sort	motility and mesenchymal features of breast cancer cells correlate with the levels and intracellular localization of transglutaminase type 2
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9f59f9c691c54a2d982335963878db74
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The Motility and Mesenchymal Features of Breast Cancer Cells Correlate with the Levels and Intracellular Localization of Transglutaminase Type 2

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