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Members of the EGF\u2010CFC family are found only in vertebrates: CFC proteins in zebrafish, <jats:italic>Xenopus<\/jats:italic>, chick, mouse and human have been characterized and indicate some common general functions in development. Cripto expression was first found in human and mouse embryonal carcinoma cells and male teratocarcinomas, and was demonstrated to be over\u2010expressed in breast, cervical, ovarian, gastric, lung, colon, and pancreatic carcinomas in contrast to normal tissues where Cripto expression was invariably low or absent. Cripto may play a role in mammary tumorigenesis, since in vitro, Cripto induces mammary cell proliferation, reduces apoptosis, increases cell migration, and inhibits milk protein expression. This prediction is strengthened by observations of Cripto expression in 80% of human and mouse mammary tumors. At least three important roles for Cripto in development have created considerable interest, and each activity may be distinct in its mechanism of receptor signaling. One role is in the patterning of the anterior\u2013posterior axis of the early embryo, a second is a crucial role in the development of the heart, and a third is in potentiating branching morphogenesis and modulating differentiation in the developing mammary gland. Whether these properties are functions of different forms of Cripto, different Cripto receptors or the distinct domains within this 15\u201338 kDa glycoprotein are examined here, but much remains to be revealed about this evolutionarily conserved gene product. Since all Cripto receptors have not yet been determined with certainty, future possible uses as therapeutic targets remain to be developed. Cripto is released or shed from expressing cells and may serve as an accessible marker gene in the early to mid\u2010progressive stages of breast and other cancers. Meanwhile some speculations on possible receptor complexes for Cripto signaling in mammary cells are offered here as a spur to further discoveries. J. Cell. Physiol. 190: 267\u2013278, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.10072","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T04:51:41Z","timestamp":1030251101000},"page":"267-278","source":"Crossref","is-referenced-by-count":60,"title":["Cripto: A tumor growth factor and more"],"prefix":"10.1002","volume":"190","author":[{"given":"Eileen D.","family":"Adamson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Minchiotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Salomon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,1,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.18.11150"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0399"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/81695"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.729"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8624"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010648923432"},{"key":"e_1_2_10_8_1","unstructured":"BiancoC AdkinsH WechselbergerC SenoM NormannoN De LucaA SunY KhanN KenneyN WilliamsK SanicolaM SalomonDS.2002.Cripto\u20101 activates Nodal and ALK4 dependent and independent signalling pathways in mammary epithelial cells. 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