Melanoma Chondroitin Sulfate Proteoglycan Enhances FAK and ERK Activation by Distinct Mechanisms

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2004 Jun 24

PMID 15210734

Citations 77

Authors

Jianbo Yang

Matthew A Price

Cheryl L Neudauer

Christopher Wilson

Soldano Ferrone

Hong Xia

Joji Iida

Melanie A Simpson

James B McCarthy

Affiliations

Soon will be listed here.

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 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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