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S100 calcium-binding protein A6 promotes epithelial-mesenchymal transition through ?-catenin in pancreatic cancer cell line.

ABSTRACT: The pathogenesis of pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. S100 calcium-binding protein A6 (S100A6) has been associated with PDAC; however, the effect of S100A6 on PDAC migration and invasion has not yet been explored. In this study, Panc-1 cells were transfected with a plasmid to induce overexpression of S100A6, and ?-catenin was knocked down using a specific short hairpin RNA (shRNA). The wound-healing and Transwell assays demonstrated that S100A6 promoted PDAC cell migration and invasion. Furthermore, ?-catenin shRNA inhibited the migration and invasion of PDAC cells. We confirmed that S100A6 induces PDAC cell migration and invasion via activation of ?-catenin in vitro. Assessment of mRNA and protein levels revealed that S100A6 induces increased expression of ?-catenin, N-cadherin and vimentin, and decreased expression of E-cadherin in PDAC cells. ?-catenin shRNA also altered the expression of epithelial-mesenchymal transition (EMT)-related markers in PDAC cells. Specifically, expression of E-cadherin was increased, whereas expression of N-cadherin and vimentin was decreased. Finally, we demonstrated that S100A6 alters the expression of EMT-related markers via ?-catenin activation. In conclusion, S100A6 induces EMT and promotes cell migration and invasion in a ?-catenin-dependent manner. S100A6 may therefore represent a novel potential therapeutic target for the treatment of pancreatic cancer.

SUBMITTER: Chen X

PROVIDER: S-EPMC4370615 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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S100 calcium-binding protein A6 promotes epithelial-mesenchymal transition through β-catenin in pancreatic cancer cell line.

Chen Xue X Liu Xinjuan X Lang Haibo H Zhang Shiqi S Luo Yanlin Y Zhang Jie J

PloS one 20150323 3

The pathogenesis of pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. S100 calcium-binding protein A6 (S100A6) has been associated with PDAC; however, the effect of S100A6 on PDAC migration and invasion has not yet been explored. In this study, Panc-1 cells were transfected with a plasmid to induce overexpression of S100A6, and β-catenin was knocked down using a specific short hairpin RNA (shRNA). The wound-healing and Transwell assays demonstrated that S100A6 promoted PDAC cell ...[more]

PMID: 25799022

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Project description:GATA6 acts as an oncogene or tumour suppressor in different cancers. Previously, we found that aberrant expression of GATA6 promoted metastasis in cholangiocarcinoma (CCA). However, the mechanism by which GATA6 promotes metastasis in CCA is unclear. In the present study, we aimed to investigate the role of GATA6 in CCA cell epithelial-mesenchymal transition (EMT). Our results showed that GATA6 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. GATA6 promoted EMT and metastasis in CCA cells in vitro and in vivo based on knockdown and overexpression analyses. ChIP-sequencing data revealed that MUC1 is a novel downstream target of GATA6. GATA6 upregulated MUC1 expression through binding to both the 1584 and 1456 GATA-motifs in the promoter region and enhancing its transcription by luciferase reporter assays and point-mutant assays. MUC1 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. In addition, MUC1 promoted EMT in CCA cells based on knockdown and overexpression analyses. Moreover, MUC1 knockdown significantly abrogated the GATA6-induced EMT in CCA cells, indicating that MUC1 promoted EMT through upregulating MUC1 in CCA cells. β-Catenin is a putative transcriptional coactivator that regulates EMT in cancers. Our data showed that MUC1 expression was positively associated with nuclear β-catenin expression in 91 CCA samples. MUC1 upregulated nuclear β-catenin expression in CCA cells. Moreover, MUC1 bound to β-catenin in CCA cells based on protein immunoprecipitation analyses. MUC1 knockdown significantly decreased the binding of MUC1 to β-catenin, and thereby decreased nuclear β-catenin protein levels in CCA cells, indicating that MUC1 bound to β-catenin and increased its nuclear expression in CCA cells. Together, our results show that GATA6 promotes EMT through MUC1/β-catenin pathway in CCA, indicating potential implications for anti-metastatic therapy.

Dataset Information

S100 calcium-binding protein A6 promotes epithelial-mesenchymal transition through ?-catenin in pancreatic cancer cell line.

Publications

S100 calcium-binding protein A6 promotes epithelial-mesenchymal transition through β-catenin in pancreatic cancer cell line.

Similar Datasets

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