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
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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