The expression of
galectin-1, one of the most important
lectins participating in the malignant
tumor development, has been shown to be regulated by
hypoxia, but its exact mechanism remains elusive. Here, we find that ectopically expressed
hypoxia-inducible factor (HIF) 1alpha
protein, an
oxygen-sensitive subunit of HIF-1 that is a master factor for cellular response to
hypoxia, significantly increases
galectin-1 expression in both
messenger RNA and
protein levels in all four
colorectal cancer (CRC) cell lines tested. However,
hypoxia-induced
galectin-1 expression cannot be seen in
sentrin/SUMO-specific
protease 1 homozygous-null mouse embryonic fibroblasts that fail to accumulate HIF-1alpha
protein. Furthermore, silence of HIF-1alpha or HIF-1beta expression by specific short hairpin RNAs (shRNAs) antagonizes
hypoxia-induced
galectin-1 expression. All these results propose that
galectin-1 is a direct target of transcriptional factor HIF-1. Applying
luciferase reporter assay and
chromatin immunoprecipitation, we identify that two
hypoxia-responsive elements located at -441 to -423 bp upstream to transcriptional start site of
galectin-1 gene are essential for HIF-1-mediated
galectin-1 expression. Finally, the knockdown of
galectin-1 by its specific
shRNA can significantly reduce
hypoxia-induced invasion and migration of CRC cell line, and the ectopic expression of
galectin-1 can remarkably restore invasion and migration abilities of HIF-1alpha-knocked SW620 cells, proposing that
galectin-1 mediates the HIF-1-induced migration and invasion of CRC cells during
hypoxia. Taken together, our results shed new light for understanding mechanism for
hypoxia/HIF-1-mediated migration/invasion of CRC cells.