title: The release of fibroblast growth factor-1 from melanoma cells requires copper ions and is mediated by phosphatidylinositol 3-kinase/Akt intracellular signaling pathway.
abstract: Melanoma is a highly invasive tumor with elevated mortality rates. Progression and aggressiveness appear related to the achievement of an angiogenic phenotype. Melanoma cells express several angiogenic factors, including fibroblast growth factor (FGF)-1 and FGF-2. The autocrine production and release of FGFs and the subsequent activation of FGF receptors, have a central role in melanoma tumor progression. We demonstrated that FGF-1 is secreted from a human melanoma cell line, A375, under conditions of serum deprivation. The release of FGF-1 is inhibited by the copper chelator ammonium tetrathiomolybdate, suggesting a role of copper in the secretory pathway, and is triggered by activation of phosphatidylinositol 3-kinase (PI3K)/Akt intracellular signaling. Interestingly, overexpression or activation of Akt has been correlated with poor prognosis in melanoma patients. Our data indicate a novel role for Akt in supporting the progression of human melanomas and advocate the need for new treatments targeting PI3K/Akt signaling pathway, to control tumor development and progression.
authors.affiliation: Department of Critical Care Medicine and Surgery, Geriatric Medicine Unit, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Serio
authors.forename: Laura
authors.initials: L
authors.lastname: Doria
authors.forename: Silvia
authors.initials: S
authors.lastname: Pellerito
authors.forename: Igor
authors.initials: I
authors.lastname: Prudovsky
authors.forename: Isabella
authors.initials: I
authors.lastname: Micucci
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Matteo
authors.initials: M
authors.lastname: Landriscina
authors.forename: Niccolò
authors.initials: N
authors.lastname: Marchionni
authors.forename: Giulio
authors.initials: G
authors.lastname: Masotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Tarantini
mesh_terms: D045744:Cell Line, Tumor; D003300:Copper / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007477:Ions; D008545:Melanoma / Q000378:metabolism*; D008982:Molybdenum / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016895:Culture Media, Serum-Free; D007477:Ions; D016220:Fibroblast Growth Factor 1; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt