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PMID: 12615911 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Differential regulation of cell motility and invasion by FAK.

The Journal of cell biology ·Vol. 160 ·No. 5 ·2003-03-03 ·Pages 753-67

Hsia DA, Mitra SK, Hauck CR, Streblow DN, Nelson JA, Ilic D, Huang S, Li E, Nemerow GR, Leng J, Spencer KS, Cheresh DA, Schlaepfer DD

Abstract

Cell migration and invasion are fundamental components of tumor cell metastasis. Increased focal adhesion kinase (FAK) expression and tyrosine phosphorylation are connected with elevated tumorigenesis. Null mutation of FAK results in embryonic lethality, and FAK-/- fibroblasts exhibit cell migration defects in culture. Here we show that viral Src (v-Src) transformation of FAK-/- cells promotes integrin-stimulated motility equal to stable FAK reexpression. However, FAK-/- v-Src cells were not invasive, and FAK reexpression, Tyr-397 phosphorylation, and FAK kinase activity were required for the generation of an invasive cell phenotype. Cell invasion was linked to transient FAK accumulation at lamellipodia, formation of a FAK-Src-p130Cas-Dock180 signaling complex, elevated Rac and c-Jun NH2-terminal kinase activation, and increased matrix metalloproteinase expression and activity. Our studies support a dual role for FAK in promoting cell motility and invasion through the activation of distinct signaling pathways.

MeSH Terms
Animals Cell Movement/genetics Cell Size/genetics Cells, Cultured Collagen/metabolism,pharmacology Crk-Associated Substrate Protein Drug Combinations Eukaryotic Cells/cytology,enzymology Fibronectins/metabolism,pharmacology Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Genetic Vectors/genetics,metabolism JNK Mitogen-Activated Protein Kinases Laminin/metabolism,pharmacology Matrix Metalloproteinase 9/genetics,metabolism Mice Mitogen-Activated Protein Kinases/genetics,metabolism Neoplasm Invasiveness/genetics Neoplasm Metastasis/genetics Oncogene Protein pp60(v-src)/genetics,metabolism Phosphoproteins/genetics,metabolism Protein-Tyrosine Kinases/deficiency,genetics Proteins Proteoglycans/metabolism,pharmacology Pseudopodia/genetics,metabolism,ultrastructure Recombinant Fusion Proteins/genetics,metabolism Retinoblastoma-Like Protein p130 Signal Transduction/genetics rac GTP-Binding Proteins/genetics,metabolism
Chemicals
Bcar1 protein, mouse Crk-Associated Substrate Protein DOCK1 protein, human Drug Combinations Fibronectins Laminin Phosphoproteins Proteins Proteoglycans Recombinant Fusion Proteins Retinoblastoma-Like Protein p130 matrigel Collagen Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Oncogene Protein pp60(v-src) Ptk2 protein, mouse JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases Matrix Metalloproteinase 9 rac GTP-Binding Proteins
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Hsia Datsun A
The Scripps Research Institute, Dept. of Immunology, IMM26, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
Mitra Satyajit K
Hauck Christof R
Streblow Daniel N
Nelson Jay A
Ilic Dusko
Huang Shuang
Li Erguang
Nemerow Glen R
Leng Jay
Spencer Kathryn S R
Cheresh David A
Schlaepfer David D
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200212114
Published
2003-03-03
Pages
753-67
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173366
Subset
IM
Grants
NCI NIH HHS · R29 CA075240 · United States
NCI NIH HHS · R01 CA087038 · United States
NCI NIH HHS · R37 CA050286 · United States
NHLBI NIH HHS · R01 HL054352 · United States
NHLBI NIH HHS · HL54352 · United States
NCI NIH HHS · CA87038 · United States
NHLBI NIH HHS · HL65754 · United States
NCI NIH HHS · R01 CA050286 · United States
NCI NIH HHS · CA50286 · United States
NCI NIH HHS · CA75240 · United States
NCI NIH HHS · P01 CA078045 · United States
NCI NIH HHS · R01 CA045726 · United States
NCI NIH HHS · R01 CA075240 · United States
NHLBI NIH HHS · R01 HL065754 · United States
NCI NIH HHS · CA78045 · United States
NCI NIH HHS · CA45726 · United States
External Links
PubMed source DOI: 10.1083/jcb.200212114 PMC Full Text View journal details
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