Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells
A type lamins are fundamental components of the nuclear lamina. Changes in lamin A expression correlate with malignant transformation in several cancers. However, the role of lamin A has not been explored in osteosarcoma (OS). Here, we wanted to investigate the role of lamin A in normal osteoblasts...
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doaj-9cfa258b67404b31b16e33f93be443792020-11-25T02:07:58ZengMDPI AGCells2073-44092020-03-019377410.3390/cells9030774cells9030774Lamin A and Prelamin a Counteract Migration of Osteosarcoma CellsCamilla Evangelisti0Francesca Paganelli1Gaia Giuntini2Elisabetta Mattioli3Alessandra Cappellini4Giulia Ramazzotti5Irene Faenza6Maria Cristina Maltarello7Alberto M. Martelli8Katia Scotlandi9Francesca Chiarini10Giovanna Lattanzi11CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza” Unit of Bologna, 40136 Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, ItalyDepartment of Molecular and Development Medicine, Cellular and Molecular Physiology Unit, University of Siena, 53100 Siena, ItalyCNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza” Unit of Bologna, 40136 Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, ItalyLaboratory of Musculoskeletal Cell Biology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, ItalyExperimental Oncology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyCNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza” Unit of Bologna, 40136 Bologna, ItalyCNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza” Unit of Bologna, 40136 Bologna, ItalyA type lamins are fundamental components of the nuclear lamina. Changes in lamin A expression correlate with malignant transformation in several cancers. However, the role of lamin A has not been explored in osteosarcoma (OS). Here, we wanted to investigate the role of lamin A in normal osteoblasts (OBs) and OS cells. Thus, we studied the expression of lamin A/C in OS cells compared to OBs and evaluated the effects of lamin A overexpression in OS cell lines. We show that, while lamin A expression increases during osteoblast differentiation, all examined OS cell lines express lower lamin A levels relative to differentiated OBs. The condition of low <i>LMNA</i> expression confers to OS cells a significant increase in migration potential, while overexpression of lamin A reduces migration ability of OS cells. Moreover, overexpression of unprocessable prelamin A also reduces cell migration. In agreement with the latter finding, OS cells which accumulate the highest prelamin A levels upon inhibition of lamin A maturation by statins, had significantly reduced migration ability. Importantly, OS cells subjected to statin treatment underwent apoptotic cell death in a RAS-independent, lamin A-dependent manner. Our results show that pro-apoptotic effects of statins and statin inhibitory effect on OS cell migration are comparable to those obtained by prelamin A accumulation and further suggest that modulation of lamin A expression and post-translational processing can be a tool to decrease migration potential in OS cells.https://www.mdpi.com/2073-4409/9/3/774osteosarcomalamin acellular migration<i>lmna</i> geneosteoblast differentiation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Camilla Evangelisti Francesca Paganelli Gaia Giuntini Elisabetta Mattioli Alessandra Cappellini Giulia Ramazzotti Irene Faenza Maria Cristina Maltarello Alberto M. Martelli Katia Scotlandi Francesca Chiarini Giovanna Lattanzi |
spellingShingle |
Camilla Evangelisti Francesca Paganelli Gaia Giuntini Elisabetta Mattioli Alessandra Cappellini Giulia Ramazzotti Irene Faenza Maria Cristina Maltarello Alberto M. Martelli Katia Scotlandi Francesca Chiarini Giovanna Lattanzi Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells Cells osteosarcoma lamin a cellular migration <i>lmna</i> gene osteoblast differentiation |
author_facet |
Camilla Evangelisti Francesca Paganelli Gaia Giuntini Elisabetta Mattioli Alessandra Cappellini Giulia Ramazzotti Irene Faenza Maria Cristina Maltarello Alberto M. Martelli Katia Scotlandi Francesca Chiarini Giovanna Lattanzi |
author_sort |
Camilla Evangelisti |
title |
Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells |
title_short |
Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells |
title_full |
Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells |
title_fullStr |
Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells |
title_full_unstemmed |
Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells |
title_sort |
lamin a and prelamin a counteract migration of osteosarcoma cells |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-03-01 |
description |
A type lamins are fundamental components of the nuclear lamina. Changes in lamin A expression correlate with malignant transformation in several cancers. However, the role of lamin A has not been explored in osteosarcoma (OS). Here, we wanted to investigate the role of lamin A in normal osteoblasts (OBs) and OS cells. Thus, we studied the expression of lamin A/C in OS cells compared to OBs and evaluated the effects of lamin A overexpression in OS cell lines. We show that, while lamin A expression increases during osteoblast differentiation, all examined OS cell lines express lower lamin A levels relative to differentiated OBs. The condition of low <i>LMNA</i> expression confers to OS cells a significant increase in migration potential, while overexpression of lamin A reduces migration ability of OS cells. Moreover, overexpression of unprocessable prelamin A also reduces cell migration. In agreement with the latter finding, OS cells which accumulate the highest prelamin A levels upon inhibition of lamin A maturation by statins, had significantly reduced migration ability. Importantly, OS cells subjected to statin treatment underwent apoptotic cell death in a RAS-independent, lamin A-dependent manner. Our results show that pro-apoptotic effects of statins and statin inhibitory effect on OS cell migration are comparable to those obtained by prelamin A accumulation and further suggest that modulation of lamin A expression and post-translational processing can be a tool to decrease migration potential in OS cells. |
topic |
osteosarcoma lamin a cellular migration <i>lmna</i> gene osteoblast differentiation |
url |
https://www.mdpi.com/2073-4409/9/3/774 |
work_keys_str_mv |
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