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The human DEK oncogene stimulates β-catenin signaling, invasion and mammosphere formation in breast cancer

Oncogene volume 30, pages 2741–2752 (2011)Cite this article

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Abstract

Breast cancer is a major cause of cancer-related deaths in American women; therefore, the identification of novel breast cancer-related molecules for the discovery of new markers and drug targets remains essential. The human DEK gene, which encodes a chromatin-binding protein and DNA topology regulator, is upregulated in many types of cancer. DEK has been implicated as an oncogene in breast cancer based on mRNA expression studies, but its functional significance in breast cancer growth and progression has not yet been tested directly. We demonstrate that DEK is highly expressed in breast cancer cells compared with normal tissue, and functionally important for cellular growth, invasion and mammosphere formation. DEK overexpression in non-tumorigenic MCF10A cells resulted in increased growth and motility, with a concomitant downregulation of E-cadherin. Conversely, DEK knockdown in MCF7 and MDA-MB-468 breast cancer cells resulted in decreased growth and motility with upregulation of E-cadherin. The use of DEK-proficient and -deficient breast cancer cells in orthotopic xenografts provided further in vivo evidence that DEK contributes to tumor growth. Activation of the β-catenin signaling pathway is important for normal and cancer stem cell character, growth and metastasis. We show that DEK expression stimulated, and DEK knockdown repressed β-catenin nuclear translocation and activity. Importantly, the expression of constitutively active β-catenin rescued breast cancer invasion defects of DEK knockdown cells. Together, our data indicate that DEK expression stimulates the growth, stem cell character and motility of breast cancer cells, and that DEK-dependent cellular invasion occurs at least in part via β-catenin activation.

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Acknowledgements

We thank Yi Zheng for critical evaluation of this manuscript. We also thank James Lessard, Aaron Zorn, Jose Cancelas, James Mulloy and James Wells for reagents and discussion, Gerard Grosveld for Dek knockout mice, Gina Kavanaugh for the immortalized Dek wild-type and knockout mouse embryonic fibroblasts and the Viral Vector Core at CCHMC. We would like to acknowledge the assistance of the Research Flow Cytometry Core in the Division of Rheumatology at Cincinnati Children's Hospital Medical Center, supported in part by NIH AR-47363. This research was supported by Kirschstein National Research Service Awards (NRSA) F32CA139931 and T32HL091805 from the National Cancer Institute (L.M.P.V.), and Public Health Service grants CA116316 (S.I.W.), CA100002 (S.E.W.), and HL079193 (K. W-B.)

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Authors and Affiliations

  1. Department of Hematology and Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    L M Privette Vinnedge & S I Wells

  2. Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    R McClaine

  3. Department of Cancer and Cell Biology, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH, USA

    P K Wagh & S E Waltz

  4. Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    K A Wikenheiser-Brokamp

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  1. L M Privette Vinnedge
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Correspondence to S I Wells.

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Privette Vinnedge, L., McClaine, R., Wagh, P. et al. The human DEK oncogene stimulates β-catenin signaling, invasion and mammosphere formation in breast cancer. Oncogene 30, 2741–2752 (2011). https://doi.org/10.1038/onc.2011.2

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