HIF1A and cancer: In middle stage LADC, HIF1A is expressed by the stimulation of hypoxia, and NOTCH1 activated by interacting with Haptoglobin, which may be secreted by the nearby cancer cells, also triggers TF HIF1α to regulate angiogenesis by the mediation of angiogenesis-related gene VEGFA and to regulate ECM remodeling and EMT by the mediation of gene LOX (Figure 6C).