Format

Send to

Choose Destination
Oncotarget. 2015 May 20;6(14):11994-2008.

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

Author information

1
Inserm, U955, Equipe 7, Créteil, France.
2
Université Paris-Est, UMR_S955, UPEC, Créteil, France.
3
Institut Curie, Centre de Recherche, CNRS UMR 3244, Paris, France.
4
Inserm, U753, Institut de Cancérologie Gustave Roussy, Villejuif, France.
5
EDST/PRASE, Rafic Harriri Campus, Faculté des Sciences, Université Libanaise, Beyrouth, Liban.
6
Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS, Créteil, France.
7
AP-HP, Hôpital H. Mondor, Département de Pathologie, Créteil, France.
8
AP-HP, Hôpital H. Mondor, Service d'urologie, Créteil, France.
9
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
10
Mouse Cancer Genetics Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

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.

KEYWORDS:

AKT; CRIPTO; EMT; FGFR; mesenchymal-like cancer cells; prostate cancer

PMID:
25596738
PMCID:
PMC4494918
DOI:
10.18632/oncotarget.2740
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center