Abstract:
:Osteosarcoma (OS) is a highly malignant bone tumour, affecting mainly children and young adults between 10 and 20 years of age. It represents the most frequent primitive malignant tumour of the skeletal system and is characterized by an extremely aggressive clinical course, with rapid development of lung metastases. In the last few years, targeting Src in the treatment of OS has become one of the major challenges in the development of new drugs, since an elevated Src kinase activity has been associated with the development and the maintenance of the OS malignant phenotype. Recently, SI-83, a novel pyrazolo[3,4-d]pyrimidine derivate Src inhibitor, was selected as a promising OS therapeutic drug because of its elevated anti-tumour effects toward human OS. In the present study, gel-based proteomics and phosphoproteomics revealed significant changes in proteins involved in many cancer related processes. We got insight into SI-83 proapoptotic and antiproliferative properties (overrepresentation of GRIA1, GRP78, and CALR and underrepresentation of NPM1, RCN, and P4HB). Nevertheless, the most significant findings of our work are the SI-83 induced dephosphorylation of ARPC5L, a subunit of the actin related Arp2/3 complex, and the decrease of other cytoskeleton proteins. These data, together with a dramatic impairment of SaOS-2 cell migration and adhesion, suggest that SI-83 may have antimetastatic features that enhance its use as a potent OS chemotherapeutic drug.
journal_name
Mol Biosystjournal_title
Molecular bioSystemsauthors
Bernardini G,Laschi M,Serchi T,Spreafico A,Botta M,Schenone S,Arena S,Geminiani M,Scaloni A,Collodel G,Orlandini M,Niccolai N,Santucci Adoi
10.1039/c3mb70328bsubject
Has Abstractpub_date
2014-06-01 00:00:00pages
1305-12issue
6eissn
1742-206Xissn
1742-2051journal_volume
10pub_type
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