title: SIN1 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition.
abstract: BACKGROUND
  Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is essential for early embryonic development and is the key regulator of Akt, which plays an important role in various pathological conditions such as cancer. However, the biological function and clinical significance of SIN1 in hepatocellular carcinoma (HCC) remains unknown.
  
  
  METHODS
  Real-time quantitative reverse-transcriptase polymerase chain reaction analysis, western blot analysis, and immunohistochemical staining were used to test the expression level of SIN1, and its correlation with clinicopathologic parameters as well as the prognosis for patients with HCC were analyzed. In addition, the biological function and molecular mechanisms of SIN1 in HCC were investigated.
  
  
  RESULTS
  SIN1 levels were elevated predominantly in HCC tissues, and its level in solitary large HCC was significantly lower than those in nodular HCC (P = .016), but showed no significant differences between solitary large HCC and small HCC (P > .05). Levels of SIN1 were up-regulated in highly metastatic HCC cell lines (HCCLM3 and MHCC97-H), whereas their invasion and migration significantly decreased after depletion of SIN1. High expression of SIN1 was associated with tumor number (P = .012), capsular formation (P = .037), and venous invasion (P = .023) and was an independent risk factor for overall survival (P = .046). Finally, SIN1 was capable of promoting invasion and metastasis of HCC by facilitating epithelial-mesenchymal transition.
  
  
  CONCLUSIONS
  The current findings suggest that SIN1 plays an important role in HCC invasion and metastasis by facilitating epithelial-mesenchymal transition.
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Xuedong
authors.initials: X
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Ruimin
authors.initials: R
authors.lastname: Chang
authors.forename: Chenchen
authors.initials: C
authors.lastname: Kong
authors.forename: Lianyue
authors.initials: L
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D034741:RNA, Small Interfering; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493277:MAPKAP1 protein, human; D034741:RNA, Small Interfering