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Loss of 11 βHSD1 enhances glycolysis, facilitates intrahepatic metastasis, and indicates poor prognosis in hepatocellular carcinoma

Lookup NU author(s): Dr Arian Laurence


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11Beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1), converting glucocorticoids from hormonally inactive cortisone to active cortisol, plays an essential role in glucose homeostasis. Accumulating evidence suggests that enhanced glycolytic activity is closely associated with postoperative recurrence and prognosis of hepatocellular carcinoma (HCC). Whether 11 beta HSD1 contributes to HCC metastasis and recurrence remains unclear. Here we found that expression of 11 beta HSD1 in human HCC (310 pairs) was frequently decreased compared to the adjacent non-neoplastic liver tissues (ANT), which correlated well with the intrahepatic-metastatic index, serum glycemia, and other malignant clinicopathological characteristics of HCC and predicted poor prognosis. Knockdown of 11 beta HSD1 in BEL-7402 cells drastically reduced the pH of culture medium and induced cell death. Meanwhile, overexpression of 11 beta HSD1 in SMMC-7721 HCC cells resulted in repression of cell migration, invasion, angiogenesis, and proliferation in vitro. When transferred into BALB/c nude mice, 11 beta HSD1 overexpression resulted in decreased intrahepatic metastasis, angiogenesis, and tumor size. F-18-2-fluoro-2-deoxyglucose accumulation assay measured by positron emission tomography elucidated that 11 beta HSD1 reduced glucose uptake and glycolysis in SMMC-7721 cells in vitro, and intrahepatic metastasis foci and subcutaneous tumor growth in vivo. We showed that 11 beta HSD1 repressed cell metastasis, angiogenesis and proliferation of HCC by causing disruption of glycolysis via the HIF-1 alpha and c-MYC pathways. In conclusion, 11 beta HSD1 inhibits the intrahepatic metastasis of HCC via restriction of tumor glycolysis activity and may serve as a prognostic biomarker for patients.

Publication metadata

Author(s): Liu X, Tan XL, Xia M, Wu C, Song J, Wu JJ, Laurence A, Xie QG, Zhang MZ, Liang HF, Zhang BX, Chen XP

Publication type: Article

Publication status: Published

Journal: Oncotarget

Year: 2016

Volume: 7

Issue: 2

Pages: 2038-2053

Online publication date: 18/12/2015

Acceptance date: 21/11/2015

ISSN (electronic): 1949-2553

Publisher: BMJ Group


DOI: 10.18632/oncotarget.6661


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Funder referenceFunder name
01-18-540085Postgraduate Innovation Fund of Doctoral Dissertation, Huazhong University of Science and Technology
2012ZX10002010-001-004State Key Project on Infection Diseases of China
2012ZX10002016-004State Key Project on Infection Diseases of China
81202300National Natural Science Foundation of China
81372327National Natural Science Foundation of China
81372495National Natural Science Foundation of China
81572427National Natural Science Foundation of China
81572855National Natural Science Foundation of China