title: Expression and functional role of CRIPTO-1 in cutaneous melanoma.
abstract: BACKGROUND
  CRIPTO-1 (CR-1) is involved in the pathogenesis and progression of human carcinoma of different histological origin. In this study we addressed the expression and the functional role of CR-1 in cutaneous melanoma.
  
  
  METHODS
  Expression of CR-1 protein in melanomas and melanoma cell lines was assessed by immunohistochemistry, western blotting and/or flow cytometry. Levels of mRNA were evaluated by real-time PCR. Invasion assays were performed in Matrigel-coated modified Boyden chambers.
  
  
  RESULTS
  Expression of CR-1 protein and/or mRNA was found in 16 out of 37 primary human cutaneous melanomas and in 12 out of 21 melanoma cell lines. Recombinant CR-1 protein activated in melanoma cells c-Src and, at lesser extent, Smad signalling. In addition, CR-1 significantly increased the invasive ability of melanoma cells that was prevented by treatment with either the ALK4 inhibitor SB-431542 or the c-Src inhibitor saracatinib (AZD0530). Anti-CR-1 siRNAs produced a significant inhibition of the growth and the invasive ability of melanoma cells. Finally, a close correlation was found in melanoma cells between the levels of expression of CR-1 and the effects of saracatinib on cell growth.
  
  
  CONCLUSIONS
  These data indicate that a significant fraction of cutaneous melanoma expresses CR-1 and that this growth factor is involved in the invasion and proliferation of melanoma cells.
authors.affiliation: Cell Biology and Biotherapy Unit, Research Department, INT-Fondazione Pascale, Naples 80131, Italy.
authors.forename: A
authors.initials: A
authors.lastname: De Luca
authors.forename: L
authors.initials: L
authors.lastname: Lamura
authors.forename: L
authors.initials: L
authors.lastname: Strizzi
authors.forename: C
authors.initials: C
authors.lastname: Roma
authors.forename: A
authors.initials: A
authors.lastname: D'Antonio
authors.forename: N
authors.initials: N
authors.lastname: Margaryan
authors.forename: G
authors.initials: G
authors.lastname: Pirozzi
authors.forename: M-Y
authors.initials: MY
authors.lastname: Hsu
authors.forename: G
authors.initials: G
authors.lastname: Botti
authors.forename: E
authors.initials: E
authors.lastname: Mari
authors.forename: M J C
authors.initials: MJ
authors.lastname: Hendrix
authors.forename: D S
authors.initials: DS
authors.lastname: Salomon
authors.forename: N
authors.initials: N
authors.lastname: Normanno
mesh_terms: D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D015153:Blotting, Western; D000081247:CSK Tyrosine-Protein Kinase; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051785:Smad Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D052117:Benzodioxoles; D004149:Dioxoles; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011799:Quinazolines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051785:Smad Proteins; C070636:TDGF1 protein, human; C515233:saracatinib; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I