title: Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms.
abstract: Melanoma chondroitin sulfate proteoglycan (MCSP) is an early cell surface melanoma progression marker implicated in stimulating tumor cell proliferation, migration, and invasion. Focal adhesion kinase (FAK) plays a pivotal role in integrating growth factor and adhesion-related signaling pathways, facilitating cell spreading and migration. Extracellular signal-regulated kinase (ERK) 1 and 2, implicated in tumor growth and survival, has also been linked to clinical melanoma progression. We have cloned the MCSP core protein and expressed it in the MCSP-negative melanoma cell line WM1552C. Expression of MCSP enhances integrin-mediated cell spreading, FAK phosphorylation, and activation of ERK1/2. MCSP transfectants exhibit extensive MCSP-rich microspikes on adherent cells, where it also colocalizes with alpha4 integrin. Enhanced activation of FAK and ERK1/2 by MCSP appears to involve independent mechanisms because inhibition of FAK activation had no effect on ERK1/2 phosphorylation. These results indicate that MCSP may facilitate primary melanoma progression by enhancing the activation of key signaling pathways important for tumor invasion and growth.
authors.affiliation: University of Minnesota, Department of Laboratory Medicine and Pathology, 312 Church St. SE, Room 7-124 BSBE, Minneapolis, MN 55406, USA.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yang
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Price
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Neudauer
authors.forename: Christopher
authors.initials: C
authors.lastname: Wilson
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Hong
authors.initials: H
authors.lastname: Xia
authors.forename: Joji
authors.initials: J
authors.lastname: Iida
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Simpson
authors.forename: James B
authors.initials: JB
authors.lastname: McCarthy
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008545:Melanoma; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D011505:Protein-Tyrosine Kinases; C101390:CSPG4 protein, human; D000099216:Chondroitin Sulfate Proteoglycan 4; C496050:PTK2 protein, human