Objective    To investigate the effects of calcium-binding protein S100 A2 on Wnt/β-catenin signaling pathway and its mechanisms.     Methods    Human osteosarcoma cell line MG63 and human colon cancer cell line HCT116 were treated with recombinant fusion protein GST-hS100A2 that was expressed in E.coli and purified.  β-catenin was quantified by Western blot and the effects of S100A2 on the β-catenin/TCF4 activity was analyzed by luciferase activity assay. The interactions between S100A2 and β-catenin/GSK-3β/DVL/Axin were detected by GST-Pulldown and Western blot.     Results    The β-catenin level in MG63 and HCT cells treated with GST-hS100A2 increased significantly as compared with that in the GST control group (P0.01). The luciferase activity in HEK 293 cells transfected with pTOP-Luc and then treated with GST-hS100A2 increased by 12.3 fold as compared with that in the GST control group (P0.01). The interactions between GST-hS100A2 and β-catenin/GSK-3β were verified by GST-Pulldown/Western blot

and no interaction was found between GST-hS100A2 and Axin/DVL.     Conclusion    S100A2 can upregulate the activity of Wnt/β-catenin signaling pathway and its mechanism may involve in the interactions between S100A2 and β-catenin/GSK-3β.