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Palladin contributes to invasive motility in human breast cancer cells

Oncogene volume 28, pages 587–598 (2009)Cite this article

Abstract

Cancer metastasis involves multiple steps including detachment of the metastatic cells from neighboring cells, the acquisition of motility and invasion to other tissue. All of these steps require the reorganization of the actin cytoskeleton. In this study, we found that the protein palladin, a molecular scaffold with an important function in actin organization, is expressed at higher overall levels in tumors compared with benign breast tissue, and also expressed significantly higher in four invasive breast cancer cell lines when compared with four non-invasive cell lines. In addition, we found that palladin plays a key role in the formation of podosomes. Podosomes are actin-rich structures that function in adhesion and matrix degradation, and have been found in many invasive cell types. Our results show that phorbol ester treatment stimulated the formation of palladin-containing podosomes in invasive, but not in non-invasive cell lines. More importantly, palladin knockdown resulted in decreased podosome formation and a significant reduction in transwell migration and invasive motility. Palladin overexpression induced podosome formation in the non-invasive MCF7 cells, which are otherwise unable to form podosomes, suggesting that palladin plays a critical role in the assembly of podosomes. Overall, these results indicate that palladin overexpression contributes to the invasive behavior of metastatic cells.

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Acknowledgements

We are grateful to the following former lab members for their assistance in the early stages of this project: Dr Mana Parast, Amir Aghajanian and Xinshuo Wang. We thank Xiaoya Ding and Dave Cowan for help with immunohistochemistry. We also thank Dr Cercina Onesto for kindly sharing the breast cancer cell lines. This work was supported by NIH Grant GM61743 (to CO). HJK was supported by NIH K08 Grant CA098240 and BB was supported by NIH training Grant CA09688.

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Authors and Affiliations

  1. Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    S M Goicoechea, H Prentice-Dunn & C A Otey

  2. Department of Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    B Bednarski & H J Kim

  3. Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    R García-Mata

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  1. S M Goicoechea
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Correspondence to S M Goicoechea.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Goicoechea, S., Bednarski, B., García-Mata, R. et al. Palladin contributes to invasive motility in human breast cancer cells. Oncogene 28, 587–598 (2009). https://doi.org/10.1038/onc.2008.408

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