Wnt5a silencing inhibits the osteosarcoma migration by suppressing PI3K/AKT signaling pathway

Abstract

Osteosarcoma is one of the most common malignant bone tumors in children and adults. Till this date, molecular mechanism behind the growth and invasiveness of osteosarcoma is poorly understood. Wnt5a plays an important role in the oncogenesis and cancer metastasis. Results show that Wnt5a has a remarkable influence on the U2OS and SaOS-2 cancer cell migration. The cell migration was dependent on the concentration of Wnt5a with low concentration (25 ng/mL) has almost no effect on the cell migration while it has remarkable influence at 100 ng/mL. The results revealed that Wnt5a can control the osteosarcoma cell migration via PI3K/Akt signalling pathways. We showed that Wnt5a activated the PI3K (p-Tyr458) and Akt phosphorylation (p-Ser473) immediately after the ligand incubation. More importantly, we demonstrated that chemotherapeutic drug like doxorubicin can effectively suppress the activity of Wnt5a ligand and thereby can inhibit the osteosar-coma cell growth and tumorigenesis. This lay the foundation for therapeutic application of Wnt5a towards the treatment of osteosarcoma.

Keywords

• Cell migration
• Doxorubicin
• Osteosarcoma
• PI3K/AKT signaling
• Wnt5a