Cox-2/PGE2 pathway can enhance the activity of HIF2-α, activate the TGF/EGFR pathway to accelerate the nuclear transfer of HIF2-α, bind to the hypoxia binding region of vascular endothelial growth factor (VEGF) and cyclin D1 encoding gene promoter, thereby mediating the progression of lung cancer [85]. Here, EPAS1 is linked to lung cancer.