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FGFR3 has tumor suppressor properties in cells with epithelial phenotype.

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.
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Submitted on : Friday, August 9, 2013 - 1:09:47 AM
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Marie Lafitte, Isabelle Moranvillier, Stéphane Garcia, Evelyne Peuchant, Juan Iovanna, et al.. FGFR3 has tumor suppressor properties in cells with epithelial phenotype.. Molecular Cancer, BioMed Central, 2013, 12 (1), pp.83. ⟨10.1186/1476-4598-12-83⟩. ⟨inserm-00850828⟩



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