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Silencing of Euchromatic Transposable Elements as a Consequence of Nuclear Lamina Dysfunction
Open AccessFeature PaperArticle

Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells

1
CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza” Unit of Bologna, 40136 Bologna, Italy
2
IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
3
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
4
Department of Molecular and Development Medicine, Cellular and Molecular Physiology Unit, University of Siena, 53100 Siena, Italy
5
Laboratory of Musculoskeletal Cell Biology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
6
Experimental Oncology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(3), 774; https://doi.org/10.3390/cells9030774
Received: 3 January 2020 / Revised: 16 March 2020 / Accepted: 19 March 2020 / Published: 22 March 2020
(This article belongs to the Collection Lamins and Laminopathies)
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 LMNA 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. View Full-Text
Keywords: osteosarcoma; lamin A; cellular migration; LMNA gene; osteoblast differentiation osteosarcoma; lamin A; cellular migration; LMNA gene; osteoblast differentiation
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MDPI and ACS Style

Evangelisti, C.; Paganelli, F.; Giuntini, G.; Mattioli, E.; Cappellini, A.; Ramazzotti, G.; Faenza, I.; Maltarello, M.C.; Martelli, A.M.; Scotlandi, K.; Chiarini, F.; Lattanzi, G. Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells. Cells 2020, 9, 774.

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