title: BTB/POZ domain-containing protein 7: epithelial-mesenchymal transition promoter and prognostic biomarker of hepatocellular carcinoma.
abstract: Epithelial-mesenchymal transition (EMT) is a critical step in the metastasis of hepatocellular carcinoma (HCC). BTB/POZ domain-containing protein 7 (BTBD7) regulates EMT-associated proteins implicated in HCC progression. However, the role(s) of BTBD7 in HCC have not been identified. Using highly metastatic HCC HCCLM3 cells, immortalized L02 hepatocytes, metastatic HCC animal models, and three independent cohorts of HCC patient specimens, we aimed to determine the involvement of BTBD7 in HCC metastasis. We show that BTBD7 messenger RNA and protein was highly expressed in HCC cells and tumor tissues, with such expression being associated with: enhanced cell motility, venous invasion, and poor prognosis. BTBD7 promoted HCC angiogenesis and metastasis in vitro and in vivo, but did not influence cell proliferation or colony formation. BTBD7 enhancement of HCC invasion and EMT phenotype occurred through activation of a RhoC-Rock2-FAK-signaling pathway, resulting in matrix metalloproteinase-2/9 production and microvessel formation. Applying a predictive risk score model, Cox regression analysis revealed that high BTBD7 expression integrated with high microvessel density was a powerful independent predictive factor of HCC clinical outcome.
  
  
  CONCLUSIONS
  The present study identifies BTBD7 as a novel candidate prognostic factor and a potential therapeutic target of HCC. (HEPATOLOGY 2013; 57:2326-2337).
authors: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, China.
authors: Yi-Ming
authors: YM
authors: Tao
authors: Jin-Lin
authors: JL
authors: Huang
authors: Shan
authors: S
authors: Zeng
authors: Sai
authors: S
authors: Zhang
authors: Xue-Gong
authors: XG
authors: Fan
authors: Zhi-Ming
authors: ZM
authors: Wang
authors: Hui-Xiang
authors: HX
authors: Yang
authors: Xiao-Hua
authors: XH
authors: Yuan
authors: Pu
authors: P
authors: Wang
authors: Fan
authors: F
authors: Wu
authors: Jia
authors: J
authors: Luo
authors: De-Yu
authors: DY
authors: Zeng
authors: Hong
authors: H
authors: Shen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C436517:BTBD7 protein, human; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020782:Matrix Metalloproteinases; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein