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Open Access Highly Accessed Research article

SOX4 interacts with plakoglobin in a Wnt3a-dependent manner in prostate cancer cells

Yu-Heng Lai12, Jessica Cheng2, Dongmei Cheng2, Mattie E Feasel2, Kyle D Beste2, Junmin Peng3456, Asma Nusrat2 and Carlos S Moreno24*

Author Affiliations

1 Program in Genetics & Molecular Biology, Emory University, Atlanta, GA 30322, USA

2 Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA

3 Department of Human Genetics, Emory Proteomics Service Center, Emory University, Atlanta, GA 30322, USA

4 Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA

5 Department of Structural Biology, St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA

6 Department of Developmental Neurobiology, St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA

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BMC Cell Biology 2011, 12:50  doi:10.1186/1471-2121-12-50

Published: 19 November 2011

Abstract

Background

SOX4 is a developmental transcription factor that is required for differentiation and proliferation in multiple tissues. SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is still not well understood. Thus, the identification of additional SOX4 binding partners is essential for elucidating the mechanism of SOX4-mediated effects in cancer progression.

Results

Here, we have adapted a one-step affinity purification method that enables rapid purification of SOX4 complexes via intracellular biotinylation of the amino-terminus of SOX4 to perform large-scale proteomics analysis. We have discovered that junction plakoglobin (JUP) interacts with SOX4 in both the cytosol and the nucleus and the interaction between SOX4 and plakoglobin is significantly increased when prostate and breast cancer cells are stimulated with WNT3A. Interactions between SOX4 and plakoglobin were further enhanced by the nuclear export inhibitor leptomycin B (LMB), suggesting that plakoglobin promotes nuclear export of SOX4. The SOX4-plakoglobin complex affected the expression of Wnt pathway target genes and SOX4 downstream targets, such as AXIN2, DICER1, and DHX9. In addition, SOX4 DNA binding activity to the promoters of DICER1, AXIN2, DHX9 and SOX4 itself was reduced by conditions that promote SOX4-plakoglobin complex formation. Conditions that enhanced SOX4-plakoglobin interactions resulted in reduced transcriptional activity of β-catenin luciferase reporters.

Conclusions

These data suggest that this newly identified interaction between SOX4 and plakoglobin is inhibitory and provides new insights into the role of SOX4 in key pathways in cell proliferation, development, and cancer progression.