Sonic hedgehog-Gli1 signaling pathway regulates the epithelial mesenchymal transition (EMT) by mediating a new target gene, S100A4, in pancreatic cancer cells
Autor: | Bin Su, Weiqi Dai, Xuan-Fu Xu, Yingqun Zhou, Fan Wang, Hua Liu, Ping Cheng, Xiaorong Xu, Chuangao Xie, Shumei Wei, Chuanyong Guo |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Male
Gene Expression lcsh:Medicine Cell Signaling Cell Movement Molecular Cell Biology Gastrointestinal Cancers Basic Cancer Research Medicine and Health Sciences RNA Small Interfering Sonic hedgehog Promoter Regions Genetic lcsh:Science Regulation of gene expression Multidisciplinary biology integumentary system S100 Proteins Middle Aged Cadherins Hedgehog signaling pathway Up-Regulation Cell biology Oncology embryonic structures Female RNA Interference Signal transduction HT29 Cells Protein Binding Signal Transduction Research Article Adult Epithelial-Mesenchymal Transition Down-Regulation Gastroenterology and Hepatology Zinc Finger Protein GLI1 Molecular Genetics Pancreatic Cancer GLI1 Cell Line Tumor Pancreatic cancer Gastrointestinal Tumors Genetics medicine Humans Vimentin Hedgehog Proteins S100 Calcium-Binding Protein A4 Gene Regulation Epithelial–mesenchymal transition Aged Binding Sites Base Sequence lcsh:R Biology and Life Sciences Computational Biology Cancers and Neoplasms Cell Biology medicine.disease Pancreatic Neoplasms biology.protein lcsh:Q Transcription Factors |
Zdroj: | PLoS ONE, Vol 9, Iss 7, p e96441 (2014) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Aims The hedgehog signaling pathway plays an important role in EMT of pancreatic cancer cells, but the precise mechanisms remain elusive. Because S100A4 as a key EMT moleculer marker was found to be upregulated upon Gli1 in pancreatic cancer cells, we focused on the relationship between Shh-Gli1 signals and S100 genes family. Methods On the base of cDNA microarray data, we investigated regulating mechanism of Gli1 to some members of S100A genes family in pancreatic cancer cell lines firstly. Then, the regulation of Gli1 to S100A4 gene was studied by molecular biology assays and the pro-metastasis effection of Gli1-dependent S100A4 was investigated in vitro. Finally, the expressions of Shh, Gli1, S100A4 and E-cadherin in pancreatic cancer tissues were studied by using immunohistochemistry assays. Results Five members of the S100 genes family, S100A2, S100A4, S100A6, S100A11, and S100A14 were found to be downregulated significantly upon Gli1 knockdown. Gli1 enhancer prediction combining with in vitro data demonstrated that Gli1 primarily regulates S100A family members via cis-acting elements. Indeed, the data indicate S100A4 and vimentin genes were upregulated significantly by Shh/Gli1-expression increasing and E-cadherin was significantly reduced at the same time. Migration of PC cells was increased significantly in a dose-dependent manner of Gli1 expression (P |
Databáze: | OpenAIRE |
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