MMP9 and neoplasm: NOTCH-2 signaling has been shown to regulate endothelial cells by activating specific MMPs, and its inhibition resulted in MMP9 upregulation and activation of PI3K-Akt signaling in gastric cancer.40 Therefore, it is possible that MMP9 overactivity may result in reduced NOTCH-2 activity, which subsequently enhances the invasive potential of tumor cells through PI3K/Akt.