Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma.
Gene expression profiling identified human melanoma cells demonstrating increased cell motility and invasiveness. The gene WNT5A best determined in vitro invasive behavior. Melanoma cells were transfected with vectors constitutively overexpressing Wnt5a. Consistent changes included actin reorganization and increased cell adhesion. No increase in beta-catenin expression or nuclear translocation was observed. There was, however, a dramatic increase in activated PKC. In direct correlation with Wnt5a expression and PKC activation, there was an increase in melanoma cell invasion. Blocking this pathway using antibodies to Frizzled-5, the receptor for Wnt5a, inhibited PKC activity and cellular invasion. Furthermore, Wnt5a expression in human melanoma biopsies directly correlated to increasing tumor grade. These observations support a role for Wnt5a in human melanoma progression.
Weeraratna
Ashani T
AT
National Human Genome Research Institute, Cancer Genetics Branch, National Institutes of Health, Bethesda, MD 20892, USA.
Jiang
Yuan
Y
Hostetter
Galen
G
Rosenblatt
Kevin
K
Duray
Paul
P
Bittner
Michael
M
Trent
Jeffrey M
JM
D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015534:Trans-Activators; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin
D000199:Actins; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin; D011493:Protein Kinase C