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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2014, Vol. 8 Issue (1) : 33-41     DOI: 10.1007/s11684-013-0301-3
REVIEW |
The impact of hypoxia in hepatocellular carcinoma metastasis
Carmen Chak-Lui Wong, Alan Ka-Lun Kai, Irene Oi-Lin Ng()
The State Key Laboratory for Liver Research and Department of Pathology, The University of Hong Kong, Hong Kong, China
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Abstract  

Hypoxia is a common phenomenon in hepatocellular carcinoma (HCC). Hypoxia stabilizes transcription factor, hypoxia-inducible factor (HIF), to activate gene transcription. Expression of HIF is closely associated with metastasis and poor prognosis in HCC. HIF mediates expression of genes that are involved in every step of HCC metastasis including epithelial-mesenchymal transition, invasion of the extracellular matrix, intravasation, extravasation, and secondar y growth of the metastases. Because HIF is the central regulator of HCC metastasis, HIF inhibitors are attractive tools when used alone or as combined treatment to curb HCC metastasis. This review will summarize the current findings on the impact of hypoxia/HIF in HCC, with a particular focus on cancer metastasis.

Keywords hypoxia      hepatocellular carcinoma (HCC)      metastasis      hypoxia-inducible factor (HIF)     
Corresponding Authors: Ng Irene Oi-Lin,Email:iolng@hku.hk   
Issue Date: 26 April 2014
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-013-0301-3     OR     http://academic.hep.com.cn/fmd/EN/Y2014/V8/I1/33
Fig.1  Hypoxia is found in regions of HCC. Immunohistochemistry staining of pimonidazole shows hypoxic regions of HCC tumor derived from HCC cells, MHCC-97L, that were orthotopically implanted in nude mice. (A) O level reduces from peripheral to central region of the HCC tumors. Hypoxic regions are commonly found in (B) peri-necrotic regions and (C) central regions of HCC.
Fig.2  Molecular biology of hypoxia. In the presence of O (normoxia), PHDs hydroxylate HIF-1α at the proline residues that are recognized by VHL, targeting HIF-1α for ubiquitin-mediated proteosomal degradation. In the absence of O (hypoxia), HIF-1α dimerizes with HIF-1β to initiate gene transcription.
Fig.3  Hypoxia and HCC metastasis. Hypoxia regulates every step of HCC metastasis by inducing genes involved in cell motility and invasion, intravasation, extravasation, and colonization of the metastatic sites.
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