title: DKK3 blocked translocation of β-catenin/EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc-3 cell.
abstract: The Wnt/β-catenin signalling pathway is activated in pancreatic cancer initiation and progression. Dickkopf-related protein 3 (DKK3) is a member of the human Dickkopf family and an antagonist of Wnt ligand activity. However, the function of DKK3 in this pathway in pancreatic cancer is rarely known. We examined the expression of DKK3 in six human pancreatic cancer cell lines, 75 pancreatic cancer and 75 adjacent non-cancerous tissues. Dickkopf-related protein 3 was frequently silenced and methylation in pancreatic cancer cell lines (3/6). The expression of DKK3 was significantly lower in pancreatic cancer tissues than in adjacent normal pancreas tissues. Further, ectopic expression of DKK3 inhibits nuclear translocation of β-catenin induced by hypoxia in pancreatic cancer Bxpc-3 cell. The forced expression of DKK3 markedly suppressed migration and the stem cell-like phenotype of pancreatic cancer Bxpc-3 cell in hypoxic conditions through reversing epithelial-mesenchymal transition (EMT). The stable expression of DKK3 sensitizes pancreatic cancer Bxpc-3 cell to gemcitabine, delays tumour growth and augments gemcitabine therapeutic effect in pancreatic cancer xenotransplantation model. Thus, we conclude from our finding that DKK3 is a tumour suppressor and improved gemcitabine therapeutic effect through inducing apoptosis and regulating β-catenin/EMT signalling in pancreatic cancer Bxpc-3 cell.
authors.affiliation: Department of Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Qingqu
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Qin
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines; D019175:DNA Methylation; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: DKK-3; EMT; chemotherapy; pancreatic cancer; β-catenin