The release of fibroblast growth factor-1 from melanoma cells requires copper ions and is mediated by phosphatidylinositol 3-kinase/Akt intracellular signaling pathway.
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.
Di Serio
Claudia
C
Department of Critical Care Medicine and Surgery, Geriatric Medicine Unit, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Doria
Laura
L
Pellerito
Silvia
S
Prudovsky
Igor
I
Micucci
Isabella
I
Massi
Daniela
D
Landriscina
Matteo
M
Marchionni
Niccolò
N
Masotti
Giulio
G
Tarantini
Francesca
F
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
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