Journal
JOURNAL OF CELL BIOLOGY
Volume 165, Issue 6, Pages 881-891Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200403174
Keywords
melanoma chondroitin sulfate proteoglycan; FAK; integrin; ERK1/2; cell spreading
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Funding
- NCI NIH HHS [R01 CA82295, P01 CA89480, R01 CA082295, P01 CA089480] Funding Source: Medline
- NCRR NIH HHS [S10 RR016851] Funding Source: Medline
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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) I 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.
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