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Role of cyclophilin B in tumorigenesis and cisplatin resistance in hepatocellular carcinoma in humans
Author(s) -
Kim Yeonghwan,
Jang Miran,
Lim Sangbin,
Won Hyeran,
Yoon KyungSik,
Park JaeHoon,
Kim Hyo Jong,
Kim ByungHo,
Park WonSang,
Ha Joohun,
Kim SungSoo
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24539
Subject(s) - hypoxia (environmental) , cancer research , hepatocellular carcinoma , in vivo , carcinogenesis , biology , colorectal cancer , hepatology , cisplatin , cancer , apoptosis , medicine , chemistry , chemotherapy , biochemistry , genetics , organic chemistry , oxygen
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. (H EPATOLOGY 2011;).