Genome-wide screening reveals an EMT molecular network mediated by Sonic hedgehog-Gli1 signaling in pancreatic cancer cells.
The role of sonic hedgehog (SHH) in epithelial mesenchymal transition (EMT) of pancreatic cancer (PC) is known, however, its mechanism is unclear. Because SHH promotes tumor development predominantly through Gli1, we sought to understand its mechanism by identifying Gli1 targets in pancreatic cancer...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3416762?pdf=render |
| _version_ | 1818619458765193216 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xuanfu Xu |
| collection | DOAJ |
| description | The role of sonic hedgehog (SHH) in epithelial mesenchymal transition (EMT) of pancreatic cancer (PC) is known, however, its mechanism is unclear. Because SHH promotes tumor development predominantly through Gli1, we sought to understand its mechanism by identifying Gli1 targets in pancreatic cancer cells.First, we investigated invasion, migration, and EMT in PC cells transfected with lentiviral Gli1 interference vectors or SHH over-expression vectors in vitro and in vivo. Next, we determined the target gene profiles of Gli1 in PC cells using cDNA microarray assays. Finally, the primary regulatory networks downstream of SHH-Gli1 signaling in PC cells were studied through functional analyses of these targets.Our results indicate there is decreased E-cadherin expression upon increased expression of SHH/Gli1. Migration of PC cells increased significantly in a dose-dependent manner within 24 hours of Gli1 expression (P<0.05). The ratio of liver metastasis and intrasplenic miniature metastasis increased markedly upon activation of SHH-Gli1 signals in nude mice. Using cDNA microarray, we identified 278 upregulated and 59 downregulated genes upon Gli1 expression in AsPC-1 cells. The data indicate that SHH-Gli1 signals promote EMT by mediating a complex signaling network including TGFβ, Ras, Wnt, growth factors, PI3K/AKT, integrins, transmembrane 4 superfamily (TM4SF), and S100A4.Our results suggest that targeting the molecular connections established between SHH-Gli1 signaling and EMT could provide effective therapies for PC. |
| first_indexed | 2024-12-16T17:37:49Z |
| format | Article |
| id | doaj.art-3db0d66cd2964e5a8e8465d943f7866c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T17:37:49Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3db0d66cd2964e5a8e8465d943f7866c2022-12-21T22:22:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4311910.1371/journal.pone.0043119Genome-wide screening reveals an EMT molecular network mediated by Sonic hedgehog-Gli1 signaling in pancreatic cancer cells.Xuanfu XuYingqun ZhouChuangao XieShu-mei WeiHuizhong GanShengli HeFan WangLing XuJie LuWeiqi DaiLei HePing ChenXingpeng WangChuanyong GuoThe role of sonic hedgehog (SHH) in epithelial mesenchymal transition (EMT) of pancreatic cancer (PC) is known, however, its mechanism is unclear. Because SHH promotes tumor development predominantly through Gli1, we sought to understand its mechanism by identifying Gli1 targets in pancreatic cancer cells.First, we investigated invasion, migration, and EMT in PC cells transfected with lentiviral Gli1 interference vectors or SHH over-expression vectors in vitro and in vivo. Next, we determined the target gene profiles of Gli1 in PC cells using cDNA microarray assays. Finally, the primary regulatory networks downstream of SHH-Gli1 signaling in PC cells were studied through functional analyses of these targets.Our results indicate there is decreased E-cadherin expression upon increased expression of SHH/Gli1. Migration of PC cells increased significantly in a dose-dependent manner within 24 hours of Gli1 expression (P<0.05). The ratio of liver metastasis and intrasplenic miniature metastasis increased markedly upon activation of SHH-Gli1 signals in nude mice. Using cDNA microarray, we identified 278 upregulated and 59 downregulated genes upon Gli1 expression in AsPC-1 cells. The data indicate that SHH-Gli1 signals promote EMT by mediating a complex signaling network including TGFβ, Ras, Wnt, growth factors, PI3K/AKT, integrins, transmembrane 4 superfamily (TM4SF), and S100A4.Our results suggest that targeting the molecular connections established between SHH-Gli1 signaling and EMT could provide effective therapies for PC.http://europepmc.org/articles/PMC3416762?pdf=render |
| spellingShingle | 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 Genome-wide screening reveals an EMT molecular network mediated by Sonic hedgehog-Gli1 signaling in pancreatic cancer cells. PLoS ONE |
| title | Genome-wide screening reveals an EMT molecular network mediated by Sonic hedgehog-Gli1 signaling in pancreatic cancer cells. |
| title_full | Genome-wide screening reveals an EMT molecular network mediated by Sonic hedgehog-Gli1 signaling in pancreatic cancer cells. |
| title_fullStr | Genome-wide screening reveals an EMT molecular network mediated by Sonic hedgehog-Gli1 signaling in pancreatic cancer cells. |
| title_full_unstemmed | Genome-wide screening reveals an EMT molecular network mediated by Sonic hedgehog-Gli1 signaling in pancreatic cancer cells. |
| title_short | Genome-wide screening reveals an EMT molecular network mediated by Sonic hedgehog-Gli1 signaling in pancreatic cancer cells. |
| title_sort | genome wide screening reveals an emt molecular network mediated by sonic hedgehog gli1 signaling in pancreatic cancer cells |
| url | http://europepmc.org/articles/PMC3416762?pdf=render |
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