Essential role of SH3GL1 in interleukin-6(IL-6)- and vascular endothelial growth factor (VEGF)-triggered p130(cas)-mediated proliferation and migration of osteosarcoma cells

摘要

We recently demonstrated that interleukin-6 (IL-6)- and vascular endothelial growth factor (VEGF)-induced osteosarcoma (OS) cell proliferation and migration are parallel to significant increased expression of SH3GL1 and the phosphorylation level of P130(cas). The expression level of SH3GL1 was widely upregulated in human OS tissues, and their overexpression was significantly correlated with more aggressive clinicopathological features. Conversely, depletion of SH3GL1 by adenovirus shRNA abrogates P130(cas) phosphorylation and IL-6- and VEGF-induced OS cell proliferation and migration. To further pinpoint the mechanism how SH3GL1 was responsible for cell proliferation and migration, we deleted SH3GL1 in vitro and in vivo. In vitro, depletion of SH3GL1 abrogates P130(cas) phosphorylation and IL-6- and VEGF-induced OS cell proliferation and migration. SH3GL1 knockdown caused cell cycle arrest in G(0)/G(1) phase via downregulation of cyclin D1, caused activation of p27(KIP), and attenuated the activation of p-Rb. Interestingly, SH3GL1 knockdown also markedly attenuated the phosphorylation level of Akt/GSK-3 beta/FAK. In vivo, depletion of SH3GL1 by shRNA inhibited the tumor tissue growth and the expression of p-P130(cas). Collectively, our results strongly suggest that SH3GL1 is a novel target for anti-osteosarcoma.