title: 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.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.|Institut Curie, Centre de Recherche, CNRS UMR 3244, Paris, France.|Inserm, U753, Institut de Cancérologie Gustave Roussy, Villejuif, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Terry
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.|EDST/PRASE, Rafic Harriri Campus, Faculté des Sciences, Université Libanaise, Beyrouth, Liban.
authors.forename: Ihsan Y
authors.initials: IY
authors.lastname: El-Sayed
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.|Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS, Créteil, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Destouches
authors.affiliation: AP-HP, Hôpital H. Mondor, Département de Pathologie, Créteil, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Maillé
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicolaiew
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|AP-HP, Hôpital H. Mondor, Service d'urologie, Créteil, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ploussard
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.
authors.forename: Fannie
authors.initials: F
authors.lastname: Semprez
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Pimpie
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Himisha
authors.initials: H
authors.lastname: Beltran
authors.affiliation: Institut Curie, Centre de Recherche, CNRS UMR 3244, Paris, France.
authors.forename: Arturo
authors.initials: A
authors.lastname: Londono-Vallejo
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.|AP-HP, Hôpital H. Mondor, Département de Pathologie, Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.|AP-HP, Hôpital H. Mondor, Service d'urologie, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Salomon
authors.affiliation: Inserm, U955, Equipe 7, Créteil, France.|Université Paris-Est, UMR_S955, UPEC, Créteil, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Vacherot
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D058851:GPI-Linked Proteins / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*
chemical_list: D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; CRIPTO; EMT; FGFR; mesenchymal-like cancer cells; prostate cancer