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

HIG2 promotes colorectal cancer progression via hypoxia-dependent and independent pathways.
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DOI:
10.1016/j.canlet.2013.07.028
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发表时间:
2013-12-01
期刊:
影响因子:
9.7
通讯作者:
DuBois, Raymond N.
DuBois, Raymond N.
中科院分区:
医学1区
文献类型:
--
作者:
Kim, Sun-Hee;Wang, Dingzhi;Park, Yun-Yong;Katoh, Hiroshi;Margalit, Ofer;Sheffer, Michal;Wu, Hong;Holla, Vijaykumar R.;Lee, Ju-Seog;DuBois, Raymond N.

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缺氧诱导基因2(hypoxia-inducible gene 2)是缺氧的生物标志物,在几种癌症中升高。在这里,我们发现,在低氧条件下,HIG 2也上调HIF-1α的表达,在常氧条件下,增强AP-1的表达,这影响了结直肠癌细胞的存活。重要的是,在小鼠原位模型中,HIGH 2的过表达通过抑制细胞凋亡促进肿瘤生长。这些结果可能与人类疾病有关,因为我们发现随着肿瘤的进展,HIG 2的表达逐渐升高。总之,这些发现表明,HIG 2在促进大肠癌生长中以缺氧依赖和独立的方式起着重要作用。
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.
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