Nuclear Lamins and Emerin Are Differentially Expressed in Osteosarcoma Cells and Scale with Tumor Aggressiveness

Abstract

The nuclear lamina is essential for the maintenance of nuclear shape and mechanics. Mutations in lamin genes have been identified in a heterogeneous spectrum of human diseases known as “laminopathies” associated with nuclear envelope defects and deregulation of cellular functions. Interestingly, osteosarcoma is the only neoplasm described in the literature in association with laminopathies. This study aims characterized the expression of A-type and B-type lamins and emerin in osteosarcoma, revealing a higher percentage of dysmorphic nuclei in osteosarcoma cells in comparison to normal osteoblasts and all the hallmarks of laminopathic features. Both lamins and emerin were differentially expressed in osteosarcoma cell lines in comparison to normal osteoblasts and correlated with tumor aggressiveness. We analysed lamin A/C expression in a tissue-microarray including osteosarcoma samples with different prognosis, finding a positive correlation between lamin A/C expression and the overall survival of osteosarcoma patients. An inefficient MKL1 nuclear shuttling and actin depolymerization, as well as a reduced expression of pRb and a decreased YAP nuclear content were observed in A-type lamin deficient 143B cells. In conclusion, we described for the first time laminopathic nuclear phenotypes in osteosarcoma cells, providing evidence for an altered lamins and emerin expression and a deregulated nucleoskeleton architecture of this tumor.

Lamin A/C Mechanosensor Drives Tumor Cell Aggressiveness and Adhesion on Substrates With Tissue-Specific Elasticity

“…In view of this, the oncogenic transformation could induce a deregulated expression of Lamin A/C in tumor cells and any alteration from its basal condition, intended as either stimulating or inhibitory, could greatly influence the homeostasis of the tumor microenvironment. In support of this, our previous work demonstrates that within osteosarcoma specimens Lamin A/C varies greatly and in dependance on cancer cell aggressiveness (Urciuoli et al, 2020). In support of our work, Evangelisti et al (2020) have confirmed that the condition of low Lamin A expression confers to osteosarcoma cells a significant increase in migration potential, while overexpression of Lamin A reduces their migration ability.…”

“…It is worth to note that although Lamin A/C deregulation has been related to cancer onset and progression (Irianto et al, 2016;Dubik and Mai, 2020), conflicting results have been achieved in dependance on the specific tumor assessed (Foster et al, 2010), making difficult to define the nature of lamin function in cancer as a favoring or counteracting factor. Indeed, lamin expression can be variable between and even within cancer subtypes, as we have recently demonstrate in osteosarcoma: our findings demonstrated that lamin expression in human osteosarcoma cells scales with tumor aggressiveness in an integrated mechanism involving MKL1 nuclear shuttling and actin polymerization, as well as pRb expression and YAP nuclear content (Urciuoli et al, 2020). Interestingly, although cancer development in laminopathic patients is a rare event, osteosarcoma is the only neoplasm associated to cases of HGPS and WS syndromes (King et al, 1978;Okamoto et al, 1997;Ishikawa et al, 2000;Shalev et al, 2007).…”

Lamin A and Prelamin A Counteract Migration of Osteosarcoma Cells

“…Low lamin A expression could cause an increase of cellular migration due to effects of lamin A absence on mechanosignaling, as recently demonstrated [50]. The reason why prelamin A accumulation reduces OS cell migration deserves further investigation.…”

Nuclear Blebbing Frequency in Tobacco-Induced Oral Potentially Malignant Disorders: A Pilot Study

“…NBs and micronuclei were noted in atypical lipomatous tumors containing chromosome 12 material, and these structures might represent a topological distribution of ring or giant marker chromosomes in the interphase nuclei [35]. Urciuoli et al [36] observed that the laminopathic phenotype in osteosarcoma tumor cells in SaOS2 (cell line) cells showed a higher variability of alterations with donut-shaped or fragmented nuclei, or NEs with blebs, septa, and folds. They showed high values of lamin B1 immunoexpression, some of the peculiar nuclear dysmorphisms so far observed in laminopathic pathological conditions.…”