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.