title: Human melanoma cells express FGFR/Src/Rho signaling that entails an adhesion-independent caveolin-1 membrane association.
abstract: Caveolae have been indicated as a center of cytoskeleton regulation for Src kinase/Rho GTPase signaling. In addition, Src recruitment on intact cortical actin cytoskeleton appears to be required for bFGF/FGFR signal activation. Recently, we established a relationship between caveolin-1 (Cav-1) expression and cell migration in human malignant melanoma, constitutively activated by a bFGF autoregulatory loop. This work intends to investigate whether caveolae's asset, through bFGF/FGFR/c-Src/Rho signaling, could be related to melanoma cell anchorage. Accordingly, we revealed the existence of a FGFR/Src kinase pathway in Cav-1 enriched detergent-resistant membranes (DRMs) of Me665/1 metastatic melanoma cells, as confirmed by FGFR silencing. Moreover, we determined the expression and phosphorylation levels of Cav-1/Src/Erk signal pathway as a function of FGFR activation and cell density. A sucrose density gradient ultracentrifugation was employed to monitor Cav-1 membrane association and buoyancy in Me665/1 cells treated for actin fragmentation or for altered phosphorylation signals. As a result, melanoma cells show remarkable resistance to Cav-1 disassembly, together with persisting cell signal activity, being Src and Cav-1 crucial modulators of Rho GTPases. In conclusion, our study primarily highlights, in a metastatic melanoma cell line expressing caveolin, the circumstances whereby caveola structural and functional endurance enables the FGFR/Src/Rho GTPases pathway to keep on cell progression.
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161-Rome, Italy.
authors: Katia
authors: K
authors: Fecchi
authors: Sara
authors: S
authors: Travaglione
authors: Francesca
authors: F
authors: Spadaro
authors: Adriano
authors: A
authors: Quattrini
authors: Isabella
authors: I
authors: Parolini
authors: Giovanni
authors: G
authors: Piccaro
authors: Carla
authors: C
authors: Raggi
authors: Alessia
authors: A
authors: Fabbri
authors: Federica
authors: F
authors: Felicetti
authors: Alessandra
authors: A
authors: Carè
authors: Carla
authors: C
authors: Fiorentini
authors: Massimo
authors: M
authors: Sargiacomo
mesh_terms: D000199:Actins / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; C495540:CAV1 protein, human; D051242:Caveolin 1; D017468:Receptors, Fibroblast Growth Factor; D019061:src-Family Kinases; D020741:rho GTP-Binding Proteins