title: Role of cyclophilin B in tumorigenesis and cisplatin resistance in hepatocellular carcinoma in humans.
abstract: Cyclophilin B (CypB) performs diverse roles in living cells, but its role in hepatocellular carcinoma (HCC) is largely unclear. To reveal its role in HCC, we investigated the induction of CypB under hypoxia and its functions in tumor cells in vitro and in vivo. Here, we demonstrated that hypoxia-inducible factor 1α (HIF-1α) induces CypB under hypoxia. Interestingly, CypB protected tumor cells, even p53-defective HCC cells, against hypoxia- and cisplatin-induced apoptosis. Furthermore, it regulated the effects of HIF-1α, including those in angiogenesis and glucose metabolism, via a positive feedback loop with HIF-1α. The tumorigenic and chemoresistant effects of CypB were confirmed in vivo using a xenograft model. Finally, we showed that CypB is overexpressed in 78% and 91% of the human HCC and colon cancer tissues, respectively, and its overexpression in these cancers reduced patient survival.
  
  
  CONCLUSIONS
  These results indicate that CypB induced by hypoxia stimulates the survival of HCC via a positive feedback loop with HIF-1α, indicating that CypB is a novel candidate target for developing chemotherapeutic agents against HCC and colon cancer.
authors: Department of Biochemistry and Molecular Biology (BK21 project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
authors: Yeonghwan
authors: Y
authors: Kim
authors: Miran
authors: M
authors: Jang
authors: Sangbin
authors: S
authors: Lim
authors: Hyeran
authors: H
authors: Won
authors: Kyung-Sik
authors: KS
authors: Yoon
authors: Jae-Hoon
authors: JH
authors: Park
authors: Hyo Jong
authors: HJ
authors: Kim
authors: Byung-Ho
authors: BH
authors: Kim
authors: Won-Sang
authors: WS
authors: Park
authors: Joohun
authors: J
authors: Ha
authors: Sung-Soo
authors: SS
authors: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D021983:Cyclophilins / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000860:Hypoxia / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016877:Oxidants; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C081786:cyclophilin B; D006861:Hydrogen Peroxide; D021983:Cyclophilins; D002945:Cisplatin