标题：ERG-SOX4 interaction promotes epithelial-mesenchymal transition in prostate cancer cells
作者机构：[Wang, L] Department of Pathology, Shandong University Medical School, #44, Wenhua Xi Rd, Jinan 250012, China, Research Center for Medicinal Biotechno 更多
通讯作者地址：[Han, B]Shandong Univ, Sch Med, Dept Pathol, 44 Wenhua Xi Rd, Jinan 250012, Peoples R China.
摘要：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. CONCLUSION 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.