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

Authors

• Jianbo Yang, University of Minnesota, Minneapolis
• Matthew A. Price, University of Minnesota, Minneapolis
• Cheryl L. Neudauer, University of Minnesota, Minneapolis
• Christopher Wilson, University of Minnesota, Minneapolis
• Soldano Ferrone, Roswell Park Cancer Institute, Buffalo, NY
• Hong Xia, University of Minnesota, Minneapolis
• Joji Iida, University of Minnesota, Minneapolis
• Melanie A. Simpson, University of Nebraska - LincolnFollow
• James B. McCarthy, University of Minnesota, Minneapolis

Document Type

Article

Date of this Version

June 2004

Comments

Copyright © 2004 The Rockefeller University Press. Published in The Journal of Cell Biology, Volume 165, Number 6, June 21, 2004 881–891 http://www.jcb.org/cgi/doi/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
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.