Analysis of Sp1-dependent adaptation mechanism of cancer cells to hypoxia for tumor microenvironment-targeted therapy

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Accumulating evidences have suggested that tumor microenvironment is an attractive target of cancer therapy. However, there are few effective strategies to accomplish it. We previously showed that FVII gene is synergistically induced under serum staved hypoxia in ovarian cancer cells. Mechnism of this transcriptional upregulation is associates with HIF2-Sp1 interaction and distinct from that of authentic hypoxia responsive genes such as VEGF. In this study, we investigated detailed mechanism of this novel transcriptional regulation. Genes regulated by similar Sp1 dependent mechanism and their function were further explored by various experiments. We found that ICAM-1 protein is robustly induced by this mechanism and contributes to growth accerelation of ovarian clear cell carcinoma cells.