Hypoxia-inducible factor-1α modulates the down-regulation of the homeodomain protein CDX2 in colorectal cancer

Hypoxia-inducible factor-1alpha (HIF-1alpha) is the main active subunit of HIF-1, which promotes tumor cell survival and critical steps involved in tumor progression and aggressiveness. To clarify the possible involvement of the HIF-1alpha subunit and homeodomain protein CDX2 in the development and progression of colorectal cancer (CRC), we examined in vivo the immunohistochemical expression of HIF-1alpha and its topological correlation with CDX2 expression in colorectal adenocarcinoma. We then examined the in vitro effect of hypoxia mimicked by CoCl2 on mRNA and protein expression of HIF-1alpha and CDX2 using two human colon cancer cell lines, SW480 and LS174T. In addition, hypoxia-induced changes in the mRNA expression of Snail were also analyzed. Of the 62 cases of CRC examined, 43 (69.4%) and 39 (62.9%) were positive for CDX2 and HIF-1alpha, respectively, such that their expression was correlated with differentiation grade, tumor stage and lymph node metastasis (chi2 test, p