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

越来越多的证据表明，肿瘤微环境是一个有吸引力的肿瘤治疗靶点。然而，很少有有效的策略来实现它。我们之前在卵巢癌细胞中发现FVII基因在血清缺氧条件下被协同诱导。这种转录上调的机制与HIF2-Sp1相互作用有关，不同于真正的缺氧反应基因，如VEGF。在这项研究中，我们研究了这种新的转录调控的详细机制。受类似Sp1依赖机制调控的基因及其功能被各种实验进一步探索。我们发现ICAM-1蛋白在这种机制下被强烈诱导，并有助于卵巢透明细胞癌细胞的生长加速。

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.