Genome-Wide Screening Reveals an EMT Molecular Network Mediated by Sonic Hedgehog-Gli1 Signaling in Pancreatic Cancer Cells

• DOI: 10.1371/journal.pone.0043119
• Publication Date: 2012-08-10T21:06:48Z
• Authors: Xuanfu Xu; Yingqun Zhou; Chuangao Xie; Shu-mei Wei; Huizhong Gan; Shengli He; Fan Wang; Ling Xu; Jie Lu; Weiqi Dai; Lei He; Ping Chen; Xingpeng Wang; Chuanyong Guo
• Keywords: GLI1

Aims The role of sonic hedgehog (SHH) in epithelial mesenchymal transition (EMT) pancreatic cancer (PC) is known, however, its mechanism unclear. Because SHH promotes tumor development predominantly through Gli1, we sought to understand by identifying Gli1 targets cells. Methods First, investigated invasion, migration, and EMT PC cells transfected with lentiviral interference vectors or over-expression vitro vivo. Next, determined the target gene profiles using cDNA microarray assays. Finally, primary regulatory networks downstream SHH-Gli1 signaling were studied functional analyses these targets. Results Our results indicate there decreased E-cadherin expression upon increased SHH/Gli1. Migration significantly a dose-dependent manner within 24 hours (P<0.05). ratio liver metastasis intrasplenic miniature markedly activation signals nude mice. Using microarray, identified 278 upregulated 59 downregulated genes AsPC-1 data that promote mediating complex network including TGFβ, Ras, Wnt, growth factors, PI3K/AKT, integrins, transmembrane 4 superfamily (TM4SF), S100A4. Conclusion suggest targeting molecular connections established between could provide effective therapies for PC.