FGFR3 has tumor suppressor properties in cells with epithelial phenotype

Molecular Cancer

Research

Benoit Rousseau¹  Geneviève Belleannée²  Pierre Dubus³  Marie Lafitte⁴  Hubert de Verneuil⁴  Sandrine Dabernat⁴  Evelyne Peuchant⁴  Aurélie Bedel⁴  Isabelle Moranvillier⁴  François Moreau-Gaudry⁵  Stéphane Garcia⁶  Juan Iovanna⁶  Véronique Guyonnet-Dupérat⁷  Jeanne Ramos⁸ 

[1] Animalerie A2, Université Bordeaux Segalen, 33076, Bordeaux, France;CHU de Bordeaux, 33051, Bordeaux, France;EA2406 Université Bordeaux Segalen, 33076, Bordeaux, France;INSERM U1035, Université Bordeaux Segalen, 146 rue Léo Saignat, 33076, Bordeaux, France;INSERM U1035, Université Bordeaux Segalen, 146 rue Léo Saignat, 33076, Bordeaux, France;Plate-forme de vectorologie, Université Bordeaux Segalen, 33076, Bordeaux, France;INSERM U1068, 13288, Marseille, France;Plate-forme de vectorologie, Université Bordeaux Segalen, 33076, Bordeaux, France;Tumorothèque de Montpellier, 34295, Montpellier, France;

关键词: FGFR3;    Pancreatic cancer;    Tumor suppressor;    Oncogene;    MAP kinases;    STAT;   

DOI  :  10.1186/1476-4598-12-83

 received in 2013-02-12, accepted in 2013-07-19,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundDue 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.ResultsFGFR3 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.ConclusionIn 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.

【 授权许可】

Unknown   
© Lafitte et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.