| First Author | Newton IP | Year | 2010 |
| Journal | Mol Biol Cell | Volume | 21 |
| Issue | 21 | Pages | 3630-8 |
| PubMed ID | 20844082 | Mgi Jnum | J:182818 |
| Mgi Id | MGI:5316929 | Doi | 10.1091/mbc.E10-04-0312 |
| Citation | Newton IP, et al. (2010) Adenomatous polyposis coli and hypoxia-inducible factor-1{alpha} have an antagonistic connection. Mol Biol Cell 21(21):3630-8 |
| abstractText | The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines the availability of beta-catenin. Another common feature of solid tumors is the presence of hypoxia as indicated by the up-regulation of hypoxia-inducible factors (HIFs) such as HIF-1alpha. Here, we demonstrate a novel link between APC and hypoxia and show that APC and HIF-1alpha antagonize each other. Hypoxia results in reduced levels of APC mRNA and protein via a HIF-1alpha-dependent mechanism. HIF-1alpha represses the APC gene via a functional hypoxia-responsive element on the APC promoter. In contrast, APC-mediated repression of HIF-1alpha requires wild-type APC, low levels of beta-catenin, and nuclear factor-kappaB activity. These results reveal down-regulation of APC as a new mechanism that contributes to the survival advantage induced by hypoxia and also show that loss of APC mutations produces a survival advantage by mimicking hypoxic conditions. |
