Notably, Varga and colleagues revealed that AKT-dependent Notch3 activation led to tumor invasion and metastasis in a Trp53ΔIECAktE17K mice model of mesenchymal CRC subtype, indicating that Notch3 may represent a potential target for patients with this CRC subtype.65 Inhibition of Notch signaling pathway by Aes, an endogenous metastasis suppressor, can block transendothelial migration and intravasation of colon cancer cells.66 Further study is needed to understand the role of Notch signaling in modulating the development of CRC. This evidence concerns the gene NOTCH3 and malignant colon neoplasm.