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Speckle-type POZ protein is negatively associated with malignancies and inhibits cell proliferation and migration in liver cancer

  • Research Article
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Tumor Biology

Abstract

Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor that is frequently mutated in human cancers. Our previous findings have indicated that SPOP is mutated and functions as a novel tumor suppressor in hepatoblastoma (HB). However, the biological roles and clinical significance of this SPOP in hepatocellular carcinoma (HCC) remain unknown. In this study, we found that the expression level of SPOP was downregulated in HCC primary tumors by quantitative real-time PCR and the protein level of SPOP was also reduced in 72 pairs of HCC tissue microarrays by immunohistochemical analyses. Moreover, SPOP expression was observed to negatively correlate with the tumor grade and intrahepatic metastasis of HCC patients. Furthermore, we revealed that SPOP not only inhibits cell proliferation but also inhibits the motility of liver cancer cells. Finally, we discovered that one of the mechanisms through which SPOP inhibits liver cancer cell migration involves the disruption of ZEB2 expression and the associated epithelial-mesenchymal transition program. Together, our findings emphasize the critical role of SPOP in the regulation of proliferation and migration in liver cancer.

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Acknowledgments

We are grateful for Dr T. Didier’s gifts of the pWPXL, psPAX2, and pMD2.G lenti-virus plasmids. This work was supported by grants from Shanghai Municipal Health Bureau (XBR2011039), Shanghai Natural Science Fund for Youth Scholars (12ZR1449900), and National Natural Science Foundation of China (81201538).

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Authors and Affiliations

  1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China

    Yuping Huang, Ying Jing, Jinjun Li & Xianghuo He

  2. Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical College, Guilin, 541004, Guangxi Province, China

    Ning Tan

  3. Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 1207 Rm., 2# Bldg., 270 Dong An Rd, Shanghai, 200032, China

    Deshui Jia, Qifeng Wang, Zhe Li, Jiwei Zhang, Li Liu, Zhiao Chen & Xianghuo He

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  1. Yuping Huang
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  8. Li Liu
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  9. Jinjun Li
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  10. Zhiao Chen
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  11. Xianghuo He
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Correspondence to Zhiao Chen or Xianghuo He.

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Huang, Y., Tan, N., Jia, D. et al. Speckle-type POZ protein is negatively associated with malignancies and inhibits cell proliferation and migration in liver cancer. Tumor Biol. 36, 9753–9761 (2015). https://doi.org/10.1007/s13277-015-3753-z

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  • DOI: https://doi.org/10.1007/s13277-015-3753-z

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