Protein phosphatase 2A Cα 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 Cα in osteosarcoma cells. PP2A Cα expression was expected to be higher in malignant osteosarcoma tissues. PP2A Cα 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 Cα-knockdown LM8 cells (shPP2A) exhibited less striking filopodial and lamellipodial structures than that in original LM8 cells. Focal adhesion kinase phosphorylation and NF-κB 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 Cα resulted in a decrease in the migration ability of LM8 cells in vitro. Reduction in PP2A Cα levels in vivo suppressed proliferation and metastasis in LM8 cells. PP2A Cα 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 Cα levels suppressed the cell proliferation rate and migration ability of MG63 cells. These results indicate that PP2A Cα has a critical role in the proliferation and metastasis of osteosarcoma cells; therefore, its inhibition could potentially suppress the malignancy of osteosarcoma cells.
Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
Di
D
Yang
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Hirohiko
H
Okamura
Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Hiroyuki
H
Morimoto
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Jumpei
J
Teramachi
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Tatsuji
T
Haneji
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D051379:Mice; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000201:enzymology*; D054648:Protein Phosphatase 2 / Q000378:metabolism*
C578496:PPP2CA protein, mouse; D054648:Protein Phosphatase 2