HIG2 promotes colorectal cancer progression via hypoxia-dependent and independent pathways

• HIG2 is highly elevated in human CRC and its level is correlated with tumor stage.
• Hypoxia-induced expression of HIG2 enhances CRC cell survival via up-regulation HIF-1α expression.
• Overexpression of HIG2 promotes CRC cell survival through activation of the AP-1 signaling pathway under normoxic conditions.

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.