title: Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1.
abstract: BACKGROUND
  Tumor invasion and metastasis are the major reasons for leading death of patients with hepatocellular carcinoma (HCC). Therefore, to identify molecules that can suppress invasion and metastasis of tumor will provide novel targets for HCC therapies. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2, TIPE2, is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice but its function in human is unclear. Our previous research has shown that TIPE2 is downregulated in human primary HCC compared with the paired adjacent non-tumor tissues.
  
  
  RESULTS
  In present study, we provide evidence that TIPE2 inhibits effectively human hepatocellular carcinoma metastasis. The forced expression of TIPE2 in HCC-derived cell lines markedly inhibits tumor cell growth, migration and invasion in vitro and suppresses growth and metastasis of HCC in vivo. Clinical information from a cohort of 112 patients reveals that loss or reduced expression of TIPE2 in primary HCC tissues is significantly associated with tumor metastasis. Mechanically, TIPE2 inhibits the migration and invasion through targeting Rac1 and then reduces F-actin polymerization and expression of matrix metallopeptidase 9 (MMP9) and urokinase plasminogen activator (uPA).
  
  
  CONCLUSIONS
  Our results indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by which it attenuates invasion and metastasis of HCC. The data suggest that TIPE2 will be a new target for HCC therapy.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan 250012, China. zhanglining@sdu.edu.cn.
authors.forename: Xuelei
authors.initials: X
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Shi
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Shen
authors.initials: S
authors.lastname: Dai
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000556:secondary; D002465:Cell Movement; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D055503:Protein Multimerization; D015398:Signal Transduction; D047368:Tumor Burden; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; C107953:RAC1 protein, human; C552057:TNFAIP8L2 protein, human; D014568:Urokinase-Type Plasminogen Activator; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D020830:rac1 GTP-Binding Protein