title: SOX4 interacts with plakoglobin in a Wnt3a-dependent manner in prostate cancer cells.
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.
authors.affiliation: Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yu-Heng
authors.initials: YH
authors.lastname: Lai
authors.forename: Jessica
authors.initials: J
authors.lastname: Cheng
authors.forename: Dongmei
authors.initials: D
authors.lastname: Cheng
authors.forename: Mattie E
authors.initials: ME
authors.lastname: Feasel
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Beste
authors.forename: Junmin
authors.initials: J
authors.lastname: Peng
authors.forename: Asma
authors.initials: A
authors.lastname: Nusrat
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Moreno
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011485:Protein Binding / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000378:metabolism*; D051185:gamma Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C491761:AXIN2 protein, human; D000903:Antibiotics, Antineoplastic; D060466:Axin Protein; D005231:Fatty Acids, Unsaturated; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D060509:Wnt3A Protein; D051185:gamma Catenin; D004247:DNA; C408087:DICER1 protein, human; D043244:Ribonuclease III; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; C038753:leptomycin B
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