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Cripto plays critical roles during embryogenesis and has been implicated in promoting the growth and spread of tumors. Cripto is required for signaling by certain transforming growth factor-2 superfamily members, such as Nodal, but also antagonizes others, such as activin.

A DNA sequence encoding the human Cripto-1 protein (comprising the signal peptide sequence and the first 139 amino acids of the mature protein, encompassing the EGF-like domain) was expressed in modified human 293 cells.

Cripto-1 is the founding member of the EGF-CFC gene family, which is conserved among vertebrates. Proteins within this family contain a signal sequence, a characteristic EGF-like domain, a cysteine-rich region termed the cryptic (CFC) motif, and a hydrophobic C terminus. It has been reported that Cripto-1 is O fucosylated on Thr-88 and that this modification is required for the physical interaction with Nodal as well as for signalling activity. We have confirmed that Cripto-1B is O-fucosylated at this site. Cripto-1 has been shown to play a critical role in the formation of the primary germ layers during gastrulation, as well as the specification of the anterior-posterior and left-right body axes in early embryonic development. During embryogenesis, cripto-1 functions as an essential co-receptor for nodal, a member of the transforming growth factor beta (TGF beta) family, to mediate transcriptional responses. The overexpression of cripto-1 has been identified in many human cancers, including breast, colon, lung, testicular, stomach, pancreatic, and ovarian cancers. The molecular mechanisms by which cripto-1 promotes tumourigenesis is unknown. However, cripto-1 has been shown to participate in in vitro transformation, migration, invasion, epithelial-to-mesenchymal transition, and branching morphogenesis in mammary epithelial cells and in breast and cervical carcinoma cells. For a review of Cripto-1, please see Strizzi L. et. al. (2005) Oncogene 24(37): 5731- 5741.