title: Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells.
abstract: OBJECTIVE
  Chronic oxidative stress from reactive oxygen species (ROS) produced by the mitochondria promotes hepatocarcinogenesis and tumor progression. However, the exact mechanism by which mitochondrial ROS contributes to tumor cell invasion is not known. We investigated the role of ROS modulator 1 (Romo1) in hepatocellular carcinoma (HCC) development and tumor cell invasiveness.
  
  
  METHODS
  We performed real-time, semi-quantitative, reverse transcriptase polymerase chain reaction; invasion and luciferase assays; and immunofluorescence and immunohistochemical analyses. The formation of pulmonary metastatic nodules after tumor cell injection was tested in severe combined immunodeficient mice. We analyzed Romo1 expression in HCC cell lines and tissues (n = 95).
  
  
  RESULTS
  Expression of Romo1 was increased in HCC cells, compared with normal human lung fibroblast cells. Exogenous expression of Romo1 in HCC cells increased their invasive activity, compared with control cells. Knockdown of Romo1 in Hep3B and Huh-7 HCC cells reduced their invasive activity in response to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Levels of Romo1 were increased compared with normal liver tissues in 63 of 95 HCC samples from patients. In HCC samples from patients, there was an inverse correlation between Romo1 overexpression and patient survival times. Increased levels of Romo1 also correlated with vascular invasion by the tumors, reduced differentiation, and larger tumor size.
  
  
  CONCLUSIONS
  Romo1 is a biomarker of HCC progression that might be used in diagnosis. Reagents that inhibit activity of Romo1 and suppress mitochondrial ROS production, rather than eliminate up-regulated intracellular ROS, might be developed as cancer therapies.
authors: Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors: Jin Sil
authors: JS
authors: Chung
authors: Sunhoo
authors: S
authors: Park
authors: Seon Ho
authors: SH
authors: Park
authors: Eun-Ran
authors: ER
authors: Park
authors: Pu-Hyeon
authors: PH
authors: Cha
authors: Bu-Yeo
authors: BY
authors: Kim
authors: Young Min
authors: YM
authors: Chung
authors: Seon Rang
authors: SR
authors: Woo
authors: Chul Ju
authors: CJ
authors: Han
authors: Sang-Bum
authors: SB
authors: Kim
authors: Kyung-Suk
authors: KS
authors: Suh
authors: Ja-June
authors: JJ
authors: Jang
authors: Kyoungbun
authors: K
authors: Lee
authors: Dong Wook
authors: DW
authors: Choi
authors: Sora
authors: S
authors: Lee
authors: Gi Young
authors: GY
authors: Lee
authors: Ki Baik
authors: KB
authors: Hahm
authors: Jung Ar
authors: JA
authors: Shin
authors: Byung Soo
authors: BS
authors: Kim
authors: Kyung Hee
authors: KH
authors: Noh
authors: Tae Woo
authors: TW
authors: Kim
authors: Kee-Ho
authors: KH
authors: Lee
authors: Young Do
authors: YD
authors: Yoo
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C513338:ROMO1 protein, human; D017382:Reactive Oxygen Species