CRIPTO overexpression promotes mesenchymal differentiation in prostate carcinoma cells through parallel regulation of AKT and FGFR activities.

Abstract

Members of the EGF-CFC (Cripto, FRL-1, Cryptic) protein family are increasingly recognized as key mediators of cell movement and cell differentiation during vertebrate embryogenesis. The founding member of this protein family, CRIPTO, is overexpressed in various human carcinomas. Yet, the biological role of CRIPTO in this setting remains unclear. Here, we find CRIPTO expression as especially high in a subgroup of primary prostate carcinomas with poorer outcome, wherein resides cancer cell clones with mesenchymal traits. Experimental studies in PCa models showed that one notable function of CRIPTO expression in prostate carcinoma cells may be to augment PI3K/AKT and FGFR1 signaling, which promotes epithelial-mesenchymal transition and sustains a mesenchymal state. In the observed signaling events, FGFR1 appears to function parallel to AKT, and the two pathways act cooperatively to enhance migratory, invasive and transformation properties specifically in the CRIPTO overexpressing cells. Collectively, these findings suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in favor of the emergence of mesenchymal-like cancer cells during the development of aggressive prostate tumors.

• Authors: Stéphane Terry, Ihsan Y El-Sayed, Damien Destouches, Pascale Maillé, Nathalie Nicolaiew, Guillaume Ploussard, Fannie Semprez, Cynthia Pimpie, Himisha Beltran, Arturo Londono-Vallejo, Yves Allory, Alexandre de la Taille, David S Salomon, Francis Vacherot
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 14 Pg. 11994-2008 (May 20 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25596738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GPI-Linked Proteins
• Intercellular Signaling Peptides and Proteins
• Neoplasm Proteins
• TDGF1 protein, human
• FGFR1 protein, human
• Receptor, Fibroblast Growth Factor, Type 1
• Proto-Oncogene Proteins c-akt

Topics

• Adenocarcinoma (metabolism, pathology)
• Animals
• Blotting, Western
• Cell Differentiation
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition (physiology)
• GPI-Linked Proteins (metabolism)
• Heterografts
• Humans
• Immunohistochemistry
• Intercellular Signaling Peptides and Proteins (metabolism)
• Male
• Mice
• Mice, Nude
• Neoplasm Proteins (metabolism)
• Prostatic Neoplasms (metabolism, pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Real-Time Polymerase Chain Reaction
• Receptor, Fibroblast Growth Factor, Type 1 (metabolism)