Open Access Research

FGFR3 has tumor suppressor properties in cells with epithelial phenotype

Marie Lafitte1, Isabelle Moranvillier1, Stéphane Garcia3, Evelyne Peuchant1, Juan Iovanna3, Benoit Rousseau4, Pierre Dubus5, Véronique Guyonnet-Dupérat2, Geneviève Belleannée6, Jeanne Ramos7, Aurélie Bedel1, Hubert de Verneuil1, François Moreau-Gaudry12 and Sandrine Dabernat1*

Author Affiliations

1 INSERM U1035, Université Bordeaux Segalen, 146 rue Léo Saignat, Bordeaux 33076, France

2 Plate-forme de vectorologie, Université Bordeaux Segalen, Bordeaux 33076, France

3 INSERM U1068, Marseille 13288, France

4 Animalerie A2, Université Bordeaux Segalen, Bordeaux 33076, France

5 EA2406 Université Bordeaux Segalen, Bordeaux 33076, France

6 CHU de Bordeaux, Bordeaux 33051, France

7 Tumorothèque de Montpellier, Montpellier 34295, France

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Molecular Cancer 2013, 12:83  doi:10.1186/1476-4598-12-83

Published: 31 July 2013

Abstract

Background

Due to frequent mutations in certain cancers, FGFR3 gene is considered as an oncogene. However, in some normal tissues, FGFR3 can limit cell growth and promote cell differentiation. Thus, FGFR3 action appears paradoxical.

Results

FGFR3 expression was forced in pancreatic cell lines. The receptor exerted dual effects: it suppressed tumor growth in pancreatic epithelial-like cells and had oncogenic properties in pancreatic mesenchymal-like cells. Distinct exclusive pathways were activated, STATs in epithelial-like cells and MAP Kinases in mesenchymal-like cells. Both FGFR3 splice variants had similar effects and used the same intracellular signaling. In human pancreatic carcinoma tissues, levels of FGFR3 dropped in tumors.

Conclusion

In tumors from epithelial origin, FGFR3 signal can limit tumor growth, explaining why the 4p16.3 locus bearing FGFR3 is frequently lost and why activating mutations of FGFR3 in benign or low grade tumors of epithelial origin are associated with good prognosis. The new hypothesis that FGFR3 can harbor both tumor suppressive and oncogenic properties is crucial in the context of targeted therapies involving specific tyrosine kinase inhibitors (TKIs). TKIs against FGFR3 might result in adverse effects if used in the wrong cell context.

Keywords:
FGFR3; Pancreatic cancer; Tumor suppressor; Oncogene; MAP kinases; STAT