Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2019; 10:4245-4246..

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

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 and Francis Vacherot

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Oncotarget. 2015; 6:11994-12008. https://doi.org/10.18632/oncotarget.2740

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Abstract

Stéphane Terry1,2,3,4, Ihsan Y. El-Sayed1,2,5, Damien Destouches1,2,6, Pascale Maillé7, Nathalie Nicolaiew1,2, Guillaume Ploussard1,9, Fannie Semprez1,2, Cynthia Pimpie1,2, Himisha Beltran8, Arturo Londono-Vallejo3, Yves Allory1,2,7, Alexandre de la Taille1,2,9,*, David S. Salomon10,*, Francis Vacherot1,2,*

1Inserm, U955, Equipe 7, Créteil, France

2Université Paris-Est, UMR_S955, UPEC, F-94000, Créteil, France

3Institut Curie, Centre de Recherche, CNRS UMR 3244, Paris, F-75248, France

4Inserm, U753, Institut de Cancérologie Gustave Roussy, F-94805, Villejuif, France

5EDST/PRASE, Rafic Harriri Campus, Faculté des Sciences, Université Libanaise, Beyrouth, Liban

6Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS, F-94010, Créteil, France

7AP-HP, Hôpital H. Mondor, Département de pathologie, F-94000, Créteil, France

8Department of Medicine, Weill Cornell Medical College, New York, NY, 10065, USA

9AP-HP, Hôpital H. Mondor, Service d’urologie, F-94000, Créteil, France

10Mouse Cancer Genetics Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA

*These authors have contributed equally to this work

Correspondence to:

Stéphane Terry, e-mail: stephane.terry@gmail.com

Keywords: prostate cancer, CRIPTO, mesenchymal-like cancer cells, EMT, FGFR, AKT

Received: August 15, 2014     Accepted: November 11, 2014     Published: January 22, 2015

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.


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