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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

CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza” Unit of Bologna, 40136 Bologna, Italy
IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
Department of Molecular and Development Medicine, Cellular and Molecular Physiology Unit, University of Siena, 53100 Siena, Italy
Laboratory of Musculoskeletal Cell Biology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
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;
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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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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