Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms
Open Access
- 21 June 2004
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 165 (6), 881-891
- https://doi.org/10.1083/jcb.200403174
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.Keywords
This publication has 56 references indexed in Scilit:
- Signal Transduction by Cell Adhesion Receptors and the Cytoskeleton: Functions of Integrins, Cadherins, Selectins, and Immunoglobulin-Superfamily MembersAnnual Review of Pharmacology and Toxicology, 2002
- Anchorage-dependent ERK signaling – mechanisms and consequencesCurrent Opinion in Genetics & Development, 2002
- The Focal Adhesion Kinase‐‐A Regulator of Cell Migration and InvasionIUBMB Life, 2002
- Melanoma Chondroitin Sulfate Proteoglycan Regulates Matrix Metalloproteinase-dependent Human Melanoma Invasion into Type I CollagenPublished by Elsevier BV ,2001
- Distinct Roles of the Adaptor Protein Shc and Focal Adhesion Kinase in Integrin Signaling to ERKPublished by Elsevier BV ,2000
- Expression of the NG2 proteoglycan enhances the growth and metastatic properties of melanoma cellsJournal of Cellular Physiology, 1998
- Integrin-mediated Activation of MAP Kinase Is Independent of FAK: Evidence for Dual Integrin Signaling Pathways in FibroblastsThe Journal of cell biology, 1997
- Signal Transduction from the Extracellular Matrix. A Role for the Focal Adhesion Protein-tyrosine Kinase FAK.Cell Structure and Function, 1996
- Localization and chemical synthesis of fibronectin peptides with melanoma adhesion and heparin binding activitiesBiochemistry, 1988
- The melanoma proteoglycan: restricted expression on microspikes, a specific microdomain of the cell surface.The Journal of cell biology, 1986