Although it seems to act in the early stages of carcinogenesis, it also plays an important role in advanced disease. Increased EPHB4 gene expression suggests an intrinsic role of EphB4 in the development of a more aggressive tumor phenotype in CRC. On the other hand, opposite findings show that expression of EphB4 is often reduced or lost in colorectal tumors. Here, EPHB4 is linked to colorectal carcinoma.