Extracellular FGF-1 Inhibits Cytoskeletal Organization and Promotes Fibroblast Motility

Qiang Ding Department of Surgery, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

Candece L. Gladson Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

Clyde R. Guidry Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

Samuel A. Santoro Department of Pathology, Division of Laboratory Medicine. School of Medicine, Washington University, St Louis, MO, 63110, USA

S. Kent Dickeson Department of Pathology, Division of Laboratory Medicine. School of Medicine, Washington University, St Louis, MO, 63110, USA

Jordan T. Shin Department of Biochemistry/Molecular Genetics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

John A. Thompson Department of Surgery, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USACorrespondence[email protected]

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Abstract

Previous efforts from this laboratory have established that acidic fibroblast growth factor (FGF-1), either added exogenously or secreted as a biologically active protein, induces a transformed phenotype in primary murine fibroblasts. Experimental studies described here demonstrate that constitutive exposure to extracellular FGF-1 results in reduced cell attachment to multiple ligands, inhibition of cytoskeletal organization, and reduced collagen contraction, despite no detectable change in integrin cell surface expression. In addition, FGF-1-transduced fibroblasts demonstrated a < 10-fold increase in migration, an observation correlated with increased tyrosine phosphorylation of p125FAK and p130CAS. Collectively, these results suggest that FGF-1-induced fibroblast transformation includes the involvement of specific FGF receptor-mediated signal transduction cascades targeted to cytoskeletal and focal adhesion structures.

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Extracellular FGF-1 Inhibits Cytoskeletal Organization and Promotes Fibroblast Motility

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Extracellular FGF-1 Inhibits Cytoskeletal Organization and Promotes Fibroblast Motility

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