Src is the representative member of the Src-family kinases (SFKs), a group of tyrosine kinases involved in several cellular processes. Its main function has been for long confined to the plasma membrane/cytoplasm compartment, being a myristoylated protein anchored to the cell membrane and functioning downstream to receptors, most of them lacking intrinsic kinase activity. In the last decades, new roles for some SFKs have been described in the nuclear compartment, suggesting that these proteins can also be involved in directly regulating gene transcription or nucleoskeleton architecture. In this review, we focused on those nuclear functions specifically attributable to Src, by considering its function as both tyrosine kinase and adapting molecule. In particular, we addressed the Src involvement in physiological as well as in pathological conditions, especially in tumors.

Mechanotransduction is a physiological process in which external mechanical stimulations are perceived, interpreted, and translated by cells into biochemical signals. Mechanical stimulations exerted by extracellular matrix stiffness and cell–cell contacts are continuously applied to living cells, thus representing a key pivotal trigger for cell homeostasis, survival, and function, as well as an essential factor for proper organ development and metabolism. Indeed, a deregulation of the mechanotransduction process consequent to gene mutations or altered functions of proteins involved in perceiving cellular and extracellular mechanics can lead to a broad range of diseases, from muscular dystrophies and cardiomyopathies to cancer development and metastatization. Here, we recapitulate the involvement of focal adhesion kinase (FAK) in the cellular conditions deriving from altered mechanotransduction processes.

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.

The measurement of biological tissues’ dielectric properties plays a crucial role in determining the state of health, and recent studies have reported microwave biosensing to be an innovative method with great potential in this field. Research has been conducted from the tissue level to the cellular level but, to date, cellular adhesion has never been considered. In addition, conventional systems for diagnosing tumor aggressiveness, such as a biopsy, are rather expensive and invasive. Here, we propose a novel microwave approach for biosensing adherent cancer cells with different malignancy degrees. A circular patch resonator was designed adjusting its structure to a standard Petri dish and a network analyzer was employed. Then, the resonator was realized and used to test two groups of different cancer cell lines, based on various tumor types and aggressiveness: low- and high-aggressive osteosarcoma cell lines (SaOS-2 and 143B, respectively), and low- and high-aggressive breast cancer cell lines (MCF-7 and MDA-MB-231, respectively). The experimental results showed that the sensitivity of the sensor was high, in particular when measuring the resonant frequency. Finally, the sensor showed a good ability to distinguish low-metastatic and high-metastatic cells, paving the way to the development of more complex measurement systems for noninvasive tissue diagnosis.