title: Speckle-type POZ protein is negatively associated with malignancies and inhibits cell proliferation and migration in liver cancer.
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.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical College, Guilin, 541004, Guangxi Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Deshui
authors.initials: D
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jing
authors.affiliation: 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.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.affiliation: 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. zachen126@126.com.
authors.forename: Zhiao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China. xhhe@fudan.edu.cn.|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. xhhe@fudan.edu.cn.
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C509761:SPOP protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
keywords: Epithelial-mesenchymal transition; Liver cancer; SPOP; Tumor suppressor