Role of zyxin in differential cell spreading and proliferation of melanoma cells and melanocytes.
Cell spreading, proliferation, and survival are modulated by focal adhesions linking extracellular matrix proteins, integrins, and the cytoskeleton. Zyxin is a focal-adhesion-associated phosphoprotein with one domain involved in the control of actin assembly and three protein-protein adapter domains implicated in the regulation of cell growth and differentiation. We characterized zyxin expression in normal human melanocytes and six melanoma cell lines in relation to cell spreading, growth, and differentiation using Western immunoblotting techniques, image analysis, flow cytometry, and confocal microscopy. We found that zyxin, focal adhesion kinase, and paxillin were significantly upregulated in melanoma cells compared to melanocytes. Zyxin expression directly related to cell spreading and proliferation and inversely related to differentiation, whereas focal adhesion kinase correlated only to cell spreading and paxillin did not significantly correlate with any of the parameters. Treatment of melanoma cells with 12-O-tetradecanoylphorbol-13-acetate downregulated zyxin expression, inhibited cell spreading and proliferation, and promoted differentiation. In contrast, 12-O-tetradecanoylphorbol-13-acetate, a mitogen for melanocytes, induced upregulation of zyxin expression in melanocytes. These findings are consistent with a role of zyxin in modulation of cell spreading, proliferation, and differentiation. Therapies directed at the downregulation of this focal adhesion phosphoprotein in melanoma cells implicate a new approach for controlling melanoma cell growth.
van der Gaag
Ellen J
EJ
Department of Dermatology, Boston University Medical School, Boston, Massachusetts 02118, USA.
Leccia
Marie-Thérèse
MT
Dekker
Sybren K
SK
Jalbert
Nicole L
NL
Amodeo
Dana M
DM
Byers
H Randolph
HR
D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006023:Glycoproteins; D006801:Humans; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008545:Melanoma / Q000473:pathology* / Q000503:physiopathology*; D008667:Metalloproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051419:Paxillin; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D060589:Zyxin
D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008667:Metalloproteins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; C092842:ZYX protein, human; D060589:Zyxin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D013755:Tetradecanoylphorbol Acetate