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Expression of FGF-2 alters focal adhesion dynamics in migration-restricted

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Abstract

Basic fibroblast growth factor (FGF-2) expression takes place during morphogenic differentiation of mammary ducts and is lost in breast cancer. Forced re-expression of FGF-2 in breast cancer cell lines induces a more differentiated phenotype and inhibits motility by unknown mechanisms. Here we demonstrate that MDA-MB-231 cells with encumbered motility due to forced re-expression of FGF-2 have activated focal complexes as determined by immunoprecipitation/western blotting and immunofluorescence staining with antibodies to FAK, p130Cas, paxillin, vinculin and phosphotyrosine. The activation of the focal adhesion complexes results in loss of stress fibers associated with malignant transformation of mammary epithelial cells and the formation of circumferentially-distributed actin bundles associated with non-transformed mammary epithelial cells. These effects require continuous FGF-2 expression, as the effects of exogenous recombinant FGF-2 are only small and transient. FGF-2 expression results in an increase in integrin α3 expression and decreases in integrin β1 and β4 expression. These changes, however, induce only a small decrease in adhesion to uncoated and fibronectin-coated tissue culture dishes suggesting that the primary cause of impaired motility is due to intrinsic signaling. These data suggest that FGF-2-inhibits motility in breast cancer cells by stabilization of focal complexes and induction of a more differentiated phenotype with disruption of stress fiber formation and a characteristic cortical actin distribution.

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Authors and Affiliations

  1. Department of Medicine, Division of Oncology/Hematology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, NJ, USA

    Reju Korah, Lydia Choi, Judith Barrios & Robert Wieder

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  1. Reju Korah
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  2. Lydia Choi
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Korah, R., Choi, L., Barrios, J. et al. Expression of FGF-2 alters focal adhesion dynamics in migration-restricted. Breast Cancer Res Treat 88, 17–28 (2004). https://doi.org/10.1007/s10459-004-6006-2

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