The Role of Cripto-1 in Cancer and Cancer Stem Cells

Cripto-1 is highly expressed in undifferentiated pluripotential human and mouse embryonic stem cells. Cripto-1 is re-expressed in a variety of human tumors, promoting cell proliferation, migration, and invasion. Cripto-1 expression is very low or absent in the adult mouse and human tissues. During embryogenesis, Cripto-1 functions as a co-receptor for TGF-β family ligands, such as Nodal, and growth and differentiation factor-1 and -3. Cripto-1 can also activate the c-src/mitogen-activated protein kinase/phosphatidylinositol 3′ kinase/Akt signaling pathway, which is strongly involved in mediating the oncogenic activity of Cripto-1. Furthermore, Cripto-1 is enriched in a stem-like cancer cell subpopulation in embryonal carcinoma, malignant melanoma, and prostate carcinoma cells. Thus, Cripto-1 has been considered to play an important role not only during early embryogenesis but also in the malignant progression of tumors. In view of that, Cripto-1 targeting therapy might have a significant potential role of targeting cancer stem cells and provide new insight into future cancer therapy.