Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms.
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.
Yang
Jianbo
J
University of Minnesota, Department of Laboratory Medicine and Pathology, 312 Church St. SE, Room 7-124 BSBE, Minneapolis, MN 55406, USA.
Price
Matthew A
MA
Neudauer
Cheryl L
CL
Wilson
Christopher
C
Ferrone
Soldano
S
Xia
Hong
H
Iida
Joji
J
Simpson
Melanie A
MA
McCarthy
James B
JB
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
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