HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 50, 48342-48350, December 13, 2002

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 277/50/48342    most recent M209481200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vadnais, J. Articles by Noël, J. Search for Related Content PubMed PubMed Citation Articles by Vadnais, J. Articles by Noël, J. Social Bookmarking                      What's this?

Autocrine Activation of the Hepatocyte Growth Factor Receptor/Met Tyrosine Kinase Induces Tumor Cell Motility by Regulating Pseudopodial Protrusion^*,

Julie Vadnais^§, Geneviève Nault^§, Zeinab Daher^§, Mohammad Amraei^¶, Yolaine Dodier, Ivan Robert Nabi^¶, and Josette Noël^**

From the  Département de physiologie, Groupe de recherche en transport membranaire, and the ^¶ Département de pathologie et biologie cellulaire, Université de Montréal, Montréal, Québec H3C 3J7, Canada

The multiple -actin rich pseudopodial protrusions of the invasive variant of Moloney sarcoma virus (MSV)-transformed epithelial MDCK cells (MSV-MDCK-INV) are strongly labeled for phosphotyrosine. Increased tyrosine phosphorylation among a number of proteins was detected in MSV-MDCK-INV cells relative to untransformed and MSV-transformed MDCK cells, especially for the hepatocyte growth factor receptor (HGF-R), otherwise known as c-met proto-oncogene. Cell surface expression of HGF-R was similar in the three cell lines, indicating that HGF-R is constitutively phosphorylated in MSV-MDCK-INV cells. Both the tyrosine kinase inhibitor herbimycin A and the HGF antibody abolished HGF-R phosphorylation, induced retraction of pseudopodial protrusions, and promoted the establishment of cell-cell contacts as well as the apparition of numerous stabilizing stress fibers in MSV-MDCK-INV cells. Furthermore, anti-HGF antibody abolished cell motility among MSV-MDCK-INV cells. Conditioned medium from MSV-MDCK-INV cells induced MDCK cell scattering, indicating that HGF is secreted by MSV-MDCK-INV cells. HGF titration followed by a subsequent washout of the antibodies led to renewed pseudopodial protrusion and cellular movement. We therefore show that activation of the tyrosine kinase activity of HGF-R/Met via an autocrine HGF loop is directly responsible for pseudopodial protrusion, thereby explaining the motile and invasive potential of this model epithelium-derived tumor cell line.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				H. C. Stuart, Z. Jia, A. Messenberg, B. Joshi, T. M. Underhill, H. Moukhles, and I. R. Nabi Localized Rho GTPase Activation Regulates RNA Dynamics and Compartmentalization in Tumor Cell Protrusions J. Biol. Chem., December 12, 2008; 283(50): 34785 - 34795. [Abstract] [Full Text] [PDF]

				S. Samane, J. Noel, Z. Charrouf, H. Amarouch, and P. S. Haddad Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts Evid. Based Complement. Altern. Med., September 1, 2006; 3(3): 317 - 327. [Abstract] [Full Text] [PDF]

				Z. Jia, L. Barbier, H. Stuart, M. Amraei, S. Pelech, J. W. Dennis, P. Metalnikov, P. O'Donnell, and I. R. Nabi Tumor Cell Pseudopodial Protrusions: LOCALIZED SIGNALING DOMAINS COORDINATING CYTOSKELETON REMODELING, CELL ADHESION, GLYCOLYSIS, RNA TRANSLOCATION, AND PROTEIN TRANSLATION J. Biol. Chem., August 26, 2005; 280(34): 30564 - 30573. [Abstract] [Full Text] [PDF]