The Mechanism Of WNT5A-mediated Migration And Invasion Of Osteosarcoma Cells

PURPOSE: WNT5 A,a representative ligand of activating several non-canonical WNT signal pathways,plays significant roles in oncogenesis and tumor inhibition.It has been shown that the non-receptor tyrosine kinase SRC is required for WNT5 Ainduced invasion of osteosarcoma cells.However,the precise molecular mechanism underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined.The study was designed to explore the role of ERK1/2 in WNT5A/SRCinduced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings.METHODS: Human osteosarcoma MG-63 cells were used.Several in vitro analyses were carried out,including Wound healing assay,Transwell migration and invasion assays,Western blot analysis,Transfection with small interfering RNA(siRNA),and Immunofluorescence assay.RESULTS: We found that WNT5A(100 ng/mL)remarkably stimulated migration and invasion of human osteosarcoma MG-63 cells,whereas inhibiting either SRC kinase activity by siRNA-mediated SRC silence or ERK1/2 phosphorylation by PD98059 treatment suppressed these effects,which suggested that the activation of SRC and ERK1/2 is essential for WNT5A-induced MG-63 cells migration and invasion.Furthermore,ERK1/2 phosphorylation induced by WNT5 A was dramatically blocked by SRC siRNA.Additionally,our study further demonstrated that MMP-14 was upregulated after exposure to WNT5 A in MG-63 cells,and the increased expression was blocked by SRC siRNA or PD98059.CONCLUSION: Collectively,these results indicate that WNT5 A activates SRC/ERK1/2 signal pathway,leading to the upregulation of MMP-14 expression and MG-63 cells migration and invasion.