Expression and therapeutic implications of cyclin-dependent kinase 4 (CDK4) in osteosarcoma

• Published in: Biochimica et biophysica acta Vol. 1864; no. 5; pp. 1573 - 1582
• Main Authors: Zhou, Yubing, Shen, Jacson K., Yu, Zujiang, Hornicek, Francis J., Kan, Quancheng, Duan, Zhenfeng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018
• Subjects: Cell cycle; Cyclin-dependent kinase 4; Osteosarcoma; Palbociclib; Rb; RNAi; CDK4; Osteosarcoma; Palbociclib; Cell cycle; TMA; siRNA; Cyclin-dependent kinase 4
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2018.02.004

Overexpression and/or hyperactivation of cyclin-dependent kinase 4 (CDK4) has been found in many types of human cancers, and a CDK4 specific inhibitor, palbociclib, has been recently approved by the FDA for the treatment of breast cancer. However, the expression and the therapeutic potential of CDK4 in osteosarcoma remain unclear. In the present study, CDK4 was found to be highly expressed in human osteosarcoma tissues and cell lines as compared with normal human osteoblasts. Elevated CDK4 expression correlated with metastasis potential and poor prognosis in osteosarcoma patients as determined by immunohistochemical analysis in a human osteosarcoma tissue microarray (TMA). CDK4 inhibition by either palbociclib or specific small interference RNA (siRNA) exhibited dose-dependent inhibition of osteosarcoma cell proliferation and growth, accompanied by suppression of the CDK4/6-cyclinD-Rb signaling pathway. Flow cytometry analysis showed that CDK4 knockdown arrested osteosarcoma cells in the G1 phase of the cell cycle and induced cell apoptosis. Furthermore, inhibition of CDK4 significantly decreased osteosarcoma cell migration in vitro determined by the wound healing assay. These data highlight that CDK4 may be a potential promising therapeutic target in the treatment of human osteosarcoma. •CDK4 is highly expressed in human osteosarcoma tissues and cell lines.•Elevated CDK4 correlates with clinicopathological features of osteosarcoma patients.•CDK4 inhibition decreases osteosarcoma cell proliferation, growth and migration.•CDK4 inhibition induces osteosarcoma cell cycle arrest and apoptosis.•CDK4 may be a promising therapeutic target for osteosarcoma treatment.