SPOP suppresses osteosarcoma invasion via PI3K/AKT/NF-κB signaling pathway

L. Chen, H. Pei, S.-J. Lu, Z.-J. Liu, L. Yan, X.-M. Zhao, B. Hu, H.-G. Lu

Department of Orthopedics, Jing Zhou Central Hospital, the Second Clinical Medical College, Yangtze University, Hubei, P.R. China. Hougenglulu@163.com

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• Oncology

OBJECTIVE:  Speckle-type POZ protein (SPOP), is an E3 ubiquitin ligase adaptor that is frequently mutated in prostate and endometrial cancers. SPOP has been shown to be responsible for oncogene SRC-3 ubiquitination and proteolysis in prostate cancers.  However, whether SPOP plays a role in osteosarcoma (OS) is unknown. In this study, we investigated the inhibitory effect of SPOP on invasion and migration of OS cells.

PATIENTS AND METHODS: Real-time PCR and Western blot were used to detect the expression of SPOP in human OS samples and cell lines. Short hairpin RNA (shRNA) was used to silencing the expression of SPOP. Small scale Real-time PCR screen was used to identify the matrix metalloproteases (MMP) family members responsible for the phenotype caused by SPOP depletion. Matrigel-coated invasion chambers were used to detect the invasion ability of SPOP in OS cells.

RESULTS:  We found that SPOP was down-regulated in clinic OS samples and cultured OS cells. Furthermore, we showed that silencing of SPOP promoted cell migratory and invasive ability of OS cells in vitro, whereas restored the expression of SPOP achieved the opposite effects. At the molecular level, we found that SPOP regulated the activity of “PI3K/Akt/NF-κB” signaling pathway in OS cells.

CONCLUSIONS: Our results suggested that down-regulation of SPOP promoted OS cells migratory and invasive ability via modulating the “PI3K/Akt/NF-κB” signaling pathway. Thus, SPOP could be a promising drug target for the treatment of OS invasion.

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