Protein Phosphatase 2a C Alpha Regulates Proliferation, Migration, And Metastasis Of Osteosarcoma Cells

Osteosarcoma is the most frequent primary bone tumor. Serine/threonine protein phosphatase 2A (PP2A) participates in regulating many important physiological processes, such as cell cycle, growth, apoptosis, and signal transduction. In this study, we examined the expression and function of PP2A C alpha in osteosarcoma cells. PP2A C alpha expression was expected to be higher in malignant osteosarcoma tissues. PP2A C alpha expression level and PP2A activity was higher in malignant osteosarcoma LM8 cells compared with that in primary osteoblasts and in the osteoblast-like cell line MC3T3-E1. Okadaic acid, an inhibitor of PP2A, reduced cell viability and induced apoptosis in LM8 cells. PP2A C alpha-knockdown LM8 cells (shPP2A) exhibited less striking filopodial and lamellipodial structures than that in original LM8 cells. Focal adhesion kinase phosphorylation and NF-kappa B activity decreased in shPP2A-treated cells. Sensitivity to serum deprivation-induced apoptosis increased in shPP2A-treated cells, accompanied by a lower expression level of anti-apoptotic BCL-2 in these cells. Reduction of PP2A C alpha resulted in a decrease in the migration ability of LM8 cells in vitro. Reduction in PP2A C alpha levels in vivo suppressed proliferation and metastasis in LM8 cells. PP2A C alpha expression was also higher in human osteosarcoma MG63 and SaOS-2 cells than that in primary osteoblasts and MC3T3-E1 cells, and reduction in PP2A C alpha levels suppressed the cell proliferation rate and migration ability of MG63 cells. These results indicate that PP2A C alpha has a critical role in the proliferation and metastasis of osteosarcoma cells; therefore, its inhibition could potentially suppress the malignancy of osteosarcoma cells.