Cripto-1: An embryonic gene that promotes tumorigenesis

Several studies have shown that cell fate regulation during embryonic development and oncogenic transformation share common regulatory mechanisms and signaling pathways. Indeed, an embryonic gene member of the EGF-Cripto-1/FRL1/ Cryptic family, Cripto-1, has been implicated in embryogenesis and in carcinogenesis. Cripto-1 together with the TGF- ligand Nodal is a key regulator of embryonic development and is a marker of undifferentiated human and mouse embryonic stem cells. While Cripto-1 expression is very low in normal adult tissues, Cripto-1 is re-expressed at high levels in several different human tumors, modulating cancer cell proliferation, migration, epithelial-to- mesenchymal transition and stimulating tumor angiogenesis. Therefore, inhibition of Cripto-1 expression using blocking antibodies or antisense expression vectors might be a useful modality not only to target fully differentiated cancer cells but also to target a subpopulation of tumor cells with stem-like characteristics.