FGF1 protects neuroblastoma SH-SY5Y cells from p53-dependent apoptosis through an intracrine pathway regulated by FGF1 phosphorylation
| Autor: | Pirou, Caroline, Montazer-Torbati, Fatemeh, Jah, Nadège, Delmas, Elisabeth, Lasbleiz, Christelle, Mignotte, Bernard, Renaud, Flore |
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| Přispěvatelé: | Laboratoire de génétique et biologie cellulaire (LGBC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Cell Death and Disease Cell Death and Disease, Nature Publishing Group, 2017, 8 (8), ⟨10.1038/cddis.2017.404⟩ Cell Death and Disease, Nature Publishing Group, 2017, 8 (8), pp.e3023-e3023. ⟨10.1038/cddis.2017.404⟩ |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2017.404⟩ |
| Popis: | International audience; Neuroblastoma, a sympathetic nervous system tumor, accounts for 15% of cancer deaths in children. In contrast to most human tumors, p53 is rarely mutated in human primary neuroblastoma, suggesting impaired p53 activation in neuroblastoma. Various studies have shown correlations between fgf1 expression levels and both prognosis severity and tumor chemoresistance. As we previously showed that fibroblast growth factor 1 (FGF1) inhibited p53-dependent apoptosis in neuron-like PC12 cells, we initiated the study of the interaction between the FGF1 and p53 pathways in neuroblastoma. We focused on the activity of either extracellular FGF1 by adding recombinant rFGF1 in media, or of intracellular FGF1 by overexpression in human SH-SY5Y and mouse N2a neuroblastoma cell lines. In both cell lines, the genotoxic drug etoposide induced a classical mitochondrial p53dependent apoptosis. FGF1 was able to inhibit p53-dependent apoptosis upstream of mitochondrial events in SH-SY5Y cells by both extracellular and intracellular pathways. Both rFGF1 addition and etoposide treatment increased fgf1 expression in SH-SY5Y cells. Conversely, rFGF1 or overexpressed FGF1 had no effect on p53-dependent apoptosis and fgf1 expression in neuroblastoma N2a cells. Using different FGF1 mutants (that is, FGF1 K132E , FGF1 S130A and FGF1 S130D), we further showed that the C-terminal domain and phosphorylation of FGF1 regulate its intracrine anti-apoptotic activity in neuroblastoma SH-SY5Y cells. This study provides the first evidence for a role of an intracrine growth factor pathway on p53-dependent apoptosis in neuroblastoma, and could lead to the identification of key regulators involved in neuroblastoma tumor progression and chemoresistance. |
| Databáze: | OpenAIRE |
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