Valosin-containing protein promotes metastasis of osteosarcoma through autophagy induction and anoikis inhibition via the ERK/NF-κß/beclin-1 signaling pathway.

ABSTRACT

Valosin-containing protein (VCP) promotes the development of metastasis in osteosarcoma (OS) via the PI3K/Akt signaling pathway. However, inhibition of the PI3K/Akt pathway does not completely reverse VCP-mediated invasion and migration of OS, suggesting that VCP-mediated OS invasion and migration involves additional mechanisms. In the present study, a positive correlation between the expression of VCP and cell autophagy was observed among OS tissues. Inhibiting VCP may decrease the survival of malignant cells; however, an autophagy stimulator may compensate for VCP inhibition and promote malignant cell survival. Altering the level of autophagy did not affect cell invasiveness or migration. ERK, NF-κß and beclin-1 protein expression levels were markedly decreased following VCP inhibition. These findings indicated that VCP may induce autophagy and enhance anoikis resistance without affecting cell invasiveness or migration. Via anoikis resistance, VCP may promote metastasis in OS. Therefore, targeting of the ERK/NF-κß/beclin-1 signaling pathway may be an effective therapeutic strategy for the management of OS.