Inhibition of Skp2 suppresses the proliferation and invasion of osteosarcoma cells

Abstract

Abstract. Osteosarcoma (OS) is a common bone tumor that mainly affects children and young adults. S-phase kinase-associated protein 2 (Skp2) has been characterized to play a critical oncogenic role in a variety of human malignancies. However, the biological function of Skp2 in OS remains largely obscure. In the present study, we elucidated the role of Skp2 in cell growth, cell cycle, apoptosis and migration in OS cells. We found that depletion of Skp2 inhibited cell growth in both MG-63 and SW 1353 cells. Moreover, we observed that depletion of Skp2 triggered cell apoptosis in two OS cell lines. Furthermore, downregulation of Skp2 induced cell cycle arrest in the G0/G1 phase in OS cells. Notably, our wound healing assay results revealed that inhibition of Skp2 suppressed cell migration in OS cells. Invariably, our western blot results demonstrated that depletion of Skp2 in OS cells inhibited activation of pAkt and increased p27 expression in OS cells, suggesting that Skp2 exerted its oncogenic function partly through the regulation of Akt and p27. Our findings revealed that targeting Skp2 could be a promising therapeutic strategy for the treatment of OS.

The role of SCFSkp2 and SCFβ‐TrCP1/2 in the cerebellar granule cell precursors

“…We found that F‐box proteins Skp2 and β‐TrCP2, which are also known to be oncoproteins, are important to maintain the proliferation of GCPs. This finding is consistent with the known role of these molecules in enhancing cell proliferation in various cancers (Ding et al., 2017; Nakayama et al., 2004; Wang et al., 2018; Zhang et al., 2016; Zhong et al., 2013). However, it is possible that other F‐box proteins are also involved in proliferation and differentiation of GCPs because approximately 70 F‐box proteins are reported in mammals.…”

WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling

“…70 ) and SKP2 (ref. 71 )) have been successfully developed using this type of enzymes. However, several E3 ubiquitin ligases such as SMURF1 , SMURF2 , ARKADIA , SYNOVIOLIN , NEDD4 , and PELLINO1 (reviewed in ref.…”

Down-regulation of Skp2 expression inhibits invasion and lung metastasis in osteosarcoma

“…During the course of our investigation, Ding and colleagues reported that overexpressing Skp2 leads to enhanced cellular growth, motility, and invasion in osteosarcoma, while increased apoptosis was observed in cell lines depleted of Skp2 42 , 43 . Although these authors did not analyze Skp2 in an in vivo model, their findings certainly corroborate our hypothesis that Skp2 plays an important oncogenic role in osteosarcoma pathobiology.…”