Abstract
HIG2 (hypoxia-inducible gene 2) is a biomarker of hypoxia and elevated in several cancers. Here, we show that HIG2 also upregulated HIF-1α expression under hypoxic conditions and enhanced AP-1 expression under normoxic conditions, which affects colorectal cancer cell survival. Importantly, over-expression of HIG2 promoted tumor growth by suppressing apoptosis in a mouse orthotopic model. These results are likely relevant to human disease since we found that the expression of HIG2 is gradually elevated as tumors progress. Collectively, these findings suggest that HIG2 plays an important role in promoting colorectal cancer growth in hypoxia-dependent and independent manners.
Keywords:
Colorectal cancer; HIF-1α; HIG2; Hypoxia; Normoxia; Survival.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Blotting, Western
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Cell Hypoxia
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Cell Line, Tumor
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Cell Survival / genetics
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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Disease Progression
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Gene Expression Regulation, Neoplastic
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HCT116 Cells
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HT29 Cells
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Heterografts / pathology
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Humans
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Hypoxia*
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Mice
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Mice, Nude
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / genetics*
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Transplantation, Heterologous
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Tumor Burden / genetics
Substances
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HIF1A protein, human
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HILPDA protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Neoplasm Proteins