title: ERG-SOX4 interaction promotes epithelial-mesenchymal transition in prostate cancer cells.
abstract: BACKGROUND
  Approximately 50% of prostate cancer (PCa) patients in Western countries harbor ERG rearrangement with concurrent ERG overexpression. Overexpression of SOX4 has been shown to play important roles in multiple cancers including PCa. However, the link between these two critical genetic aberrations was unclear.
  
  
  METHODS
  Fluorescence in situ hybridization and immunohistochemistry were utilized to detect ERG rearrangement and SOX4 expression. Cellular function was evaluated by transwell, wound healing assays, and cell adhesion assay, respectively. Interaction between ERG and SOX4 was arrayed by co-immunoprecipitation, Real-time PCR, Western blot, and siRNA. Direct binding of ERG to the promoter of SOX4, as well as epigenetic modifications of their promoters after TGF-β1 treatment was monitored by chromatin immunoprecipitation.
  
  
  RESULTS
  ERG regulated SOX4 expression via binding to its promoter. Silencing both of them showed duplicate effects on restoring the epithelial characteristics, increasing cellular adhesion and decreasing capacity of cellular migration and invasion. ERG and SOX4 have cooperative roles in TGF-β1-induced epithelial to mesenchymal transition (EMT) process. In addition, TGF-β1 stimulation increased levels of chromatin marks associated with active genes (H3K4me3, H416ac), and decreased levels of repressive marks (H3K27me3) at their promoters. 5-aza and TSA treatment changed expressions of ERG and SOX4. Clinically, overexpression of SOX4 is associated with ERG rearrangement status in PCa and ERG+/SOX4+ defined a subset of PCa patients with poor prognosis.
  
  
  CONCLUSIONS
  Our findings define a key role for ERG/SOX4 in the development of a subset of PCa and highlight the clinical importance of identifying molecularly defined tumor subgroups.
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, China; Research Center for Medicinal Biotechnology, Shandong Academy of Medicinal Sciences, Jinan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Yanjiang
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yang
authors.forename: Huiqing
authors.initials: H
authors.lastname: Yuan
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Qi
authors.forename: Yannicca W Y
authors.initials: YW
authors.lastname: Chang
authors.forename: Chunni
authors.initials: C
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fu
authors.forename: Muyi
authors.initials: M
authors.lastname: Yang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Han
mesh_terms: D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: C072312:ERG protein, human; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D053773:Transforming Growth Factor beta1
keywords: EMT; ERG; SOX4; TGF-β1; prostate cancer