title: S100 calcium-binding protein A6 promotes epithelial-mesenchymal transition through β-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 β-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, β-catenin shRNA inhibited the migration and invasion of PDAC cells. We confirmed that S100A6 induces PDAC cell migration and invasion via activation of β-catenin in vitro. Assessment of mRNA and protein levels revealed that S100A6 induces increased expression of β-catenin, N-cadherin and vimentin, and decreased expression of E-cadherin in PDAC cells. β-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 β-catenin activation. In conclusion, S100A6 induces EMT and promotes cell migration and invasion in a β-catenin-dependent manner. S100A6 may therefore represent a novel potential therapeutic target for the treatment of pancreatic cancer.
authors: Department of Gastroenterology, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors: Xue
authors: X
authors: Chen
authors: Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors: Xinjuan
authors: X
authors: Liu
authors: Department of Gastroenterology, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors: Haibo
authors: H
authors: Lang
authors: Department of Gastroenterology, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors: Shiqi
authors: S
authors: Zhang
authors: Department of neurobiology and Beijing institute for brain disorders, School of basic medical science, Capital Medical University, Beijing, China.
authors: Yanlin
authors: Y
authors: Luo
authors: Department of Gastroenterology, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors: Jie
authors: J
authors: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; D051176:beta Catenin; C055351:S100A6 protein, human