MMP9 and neoplasm: Taken together, it seems that Notch1 and its signaling pathways such as PI3k-Akt and MMP9 play a significant role in tumor angiogenesis with the help of VEGF and HIF1-α factors; admittedly, the presence of hypoxia plays a significant role in exacerbating angiogenesis, and in normoxia, less pro-angiogenic factors will be present.