Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms

Jianbo Yang, Matthew A. Price, Cheryl L. Neudauer, Christopher Wilson, Soldano Ferrone, Hong Xia, Joji Iida, Melanie A. Simpson, James B. McCarthy

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107 Scopus citations

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 α4 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.

Original languageEnglish (US)
Pages (from-to)881-891
Number of pages11
JournalJournal of Cell Biology
Volume165
Issue number6
DOIs
StatePublished - Jun 21 2004

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Keywords

  • Cell spreading
  • ERK1/2
  • FAK
  • Integrin
  • Melanoma chondroitin sulfate proteoglycan

ASJC Scopus subject areas

  • Cell Biology

Cite this

Yang, J., Price, M. A., Neudauer, C. L., Wilson, C., Ferrone, S., Xia, H., Iida, J., Simpson, M. A., & McCarthy, J. B. (2004). Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms. Journal of Cell Biology, 165(6), 881-891. https://doi.org/10.1083/jcb.200403174