Osteosarcoma (OS) is a fatal form of musculoskeletal tumor that commonly leads to pulmonary metastatic disease. Traditional therapies such as surgery and chemotherapy are not effective treatment modalities in certain patients with OS; therefore, identifying the molecular mechanism of OS is imperative for the development of novel therapeutics. Previous studies have reported that focal adhesion kinase (FAK) is associated with numerous types of human malignancies. Therefore, in order to investigate the biological function of FAK in OS, the present study examined the expression levels of FAK in OS cell lines, OS tissues and paired normal tissue specimens by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). FAK expression in vitro was blocked using small interfering RNA (siRNA) to observe the invasion, proliferation and apoptosis trends of OS cells. Phosphoinositide-dependent kinase-1 (PDK1), AKT and BRAF protein levels were also evaluated by western blotting to analyze the effects of FAK depletion on the AKT and mitogen-activated protein kinase (MAPK) signaling pathways. A significantly reduced level of FAK mRNA was identified in paired normal tissues compared with OS tissues and cell lines. The invasive capability and proliferative potential of OS cells were suppressed due to the transient in vitro transfection of FAK siRNA. It was also demonstrated that decreased FAK expression facilitated the apoptosis of OS cells, as demonstrated by flow cytometric and western blotting analyses. Decreased FAK expression resulted in the downregulation of phosphorylated (p)-AKT, p-PDK1 and p-BRAF protein levels. Higher FAK expression levels are positively associated with clinicopathological characteristics of advanced Enneking stages (P<0.001) and recurrence (P=0.041) in patients with OS. Collectively, these data demonstrated that FAK is an important diagnostic biomarker for OS, and FAK siRNA therapy may be a potentially promising approach for the treatment of OS.
Keywords: focal adhesion kinase; migration; osteosarcoma; prognosis; proliferation.