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Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells

Oncogene volume 20, pages 1152–1163 (2001)Cite this article

Abstract

Focal adhesion kinase (FAK) has been implicated in the regulation of cell migration. In addition, FAK expression is increased in a number of highly metastatic tumor cell lines. Therefore, we investigated the role of FAK in regulating migration of prostate carcinoma cell lines with increasing metastatic potential. We show that highly tumorigenic PC3 and DU145 cells exhibit intrinsic migratory capacity, while poorly tumorigenic LNCaP cells require a stimulus to migrate. Increased metastatic potential of PC3 and DU145 cells correlates with increased FAK expression, overall tyrosine phosphorylation and activity, as measured by autophosphorylation of tyrosine 397. However, in PC3 and DU145 cells, FAK autophosphorylation is adhesion dependent whereas a second site of tyrosine phosphorylation, tyrosine 861, a Src specific site, is uncoupled from adhesion-dependent signaling events. Finally, inhibiting the FAK/Src signal transduction pathway by over expressing FRNK (Focal adhesion kinase-Related Non-Kinase), an inhibitor of FAK activation, or treatment with PP2, a Src family kinase inhibitor, significantly inhibited migration of prostate carcinoma cell lines, demonstrating that tumor cell migration continues to be dependent on signals emanating from this pathway.

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Acknowledgements

We thank Dr Lelund Chung for the prostate cell lines and Dr Steve Hardy for the Adenovirus vector. We are grateful to Dr Gina Petroni from the University of Virginia Cancer Center Biostatistics Core for assistance with the statistical analysis. This work was supported by DHHS-NCI grant P01 CA76465, and a Research Award from CaP CURE.

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Authors and Affiliations

  1. Department of Microbiology, University of Virginia, Charlottesville, 22908, Virginia, VA, USA

    Jill K Slack, Catherine E Stoker & J Thomas Parsons

  2. Department of Surgery, University of Virginia, Charlottesville, 22908, Virginia, VA, USA

    Reid B Adams & Joshua D Rovin

  3. Department of Health Evaluation Sciences, University of Virginia, Charlottesville, 22908, Virginia, VA, USA

    Eric A Bissonette

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  1. Jill K Slack
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Slack, J., Adams, R., Rovin, J. et al. Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells. Oncogene 20, 1152–1163 (2001). https://doi.org/10.1038/sj.onc.1204208

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