Article abstract
Nature Cell Biology 1, 507 - 513 (1999)
Published online: 10 November 1999 | doi:10.1038/70302
Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas
Kathryn M. Eisenmann1, James B. McCarthy1,2,3, Melanie A. Simpson1, Patricia J. Keely5, Jun-Lin Guan4, Kouichi Tachibana6, Louis Lim7, Ed Manser8, Leo T. Furcht1,2 & Joji Iida1,3
Abstract
Melanoma chondroitin sulphate proteoglycan (MCSP) is a cell-surface antigen
that has been implicated in the growth and invasion of melanoma tumours. Although
this antigen is expressed early in melanoma progression, its biological function
is unknown. MCSP can stimulate the integrin-
4
1-mediated adhesion and spreading of melanoma cells. Here
we show that stimulated MCSP recruits tyrosine-phosphorylated p130
cas, an adaptor protein important in tumour cell motility and invasion.
MCSP stimulation also results in a pronounced activation and recruitment of
the Rho-family GTPase Cdc42. MCSP-induced spreading of melanoma cells is dependent
upon active Cdc42, a Cdc42-associated tyrosine kinase (Ack-1) and tyrosine
phosphorylation of p130cas. Furthermore, vectors inhibiting
Ack-1 or Cdc42 expression and/or function abrogate MCSP-induced tyrosine phosphorylation
and recruitment of p130cas. Our findings indicate that MCSP
may modify tumour growth or invasion by a unique signal-transduction pathway
that links Cdc42 activation to downstream tyrosine phosphorylation and subsequent
cytoskeletal reorganization.
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA
- Biomedical Engineering Institute, University of Minnesota , Minneapolis, Minnesota 55455, USA
- Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA
- Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA
- Department of Pharmacology, University of Wisconsin , Madison, Wisconsin 53706, USA
- Department of Cancer Immunology and AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA
- Institute of Neurology, London WC1N 1PJ, UK
- Institute of Molecular and Cell Biology, National University of Singapore, 15 Lower Kent Ridge Road, 119076 Singapore
Correspondence to: James B. McCarthy1,2,3 e-mail: mccar001@tc.umn.edu
