title: Embigin is overexpressed in pancreatic ductal adenocarcinoma and regulates cell motility through epithelial to mesenchymal transition via the TGF-β pathway.
abstract: Embigin is a member of the immunoglobulin superfamily and encodes a transmembrane glycoprotein. There have been reports of Embigin involvement in neuromuscular junction formation and plasticity; however, the molecular functions of Embigin in other organs are unknown. Our aim was to investigate the possible role of Embigin in pancreatic cancer. In pancreatic ductal adenocarcinoma tissues, Embigin expression was higher than that in normal pancreatic tissues. Immunohistochemical analysis revealed expression of Embigin in pancreatic cancer cells, as well as expression of monocarboxylate transporter 2 (MCT2) in cancer tissues. To gain further insight, we transfected BxPC-3 and HPAC pancreatic cancer cells with siRNA or shRNA targeting Embigin and observed reductions in cell proliferation, migration, invasion, wound healing, and reduced levels of matrix metalloproteinases-2 and -9. Silencing of Embigin increased intracellular L-lactate concentration by 1.5-fold and decreased MCT2 levels at the plasma membrane. Furthermore, Embigin silencing led to a reduced expression of PI3K, GSK3-β, and Snail/Slug. Upon treating BxPC-3 cells with transforming growth factor-β (TGF-β), we observed elevated expression of Snail/Slug, Embigin, and Vimentin; meanwhile, when treating cells with SB-216763, a GSK3-β inhibitor, we noted decreases in GSK3-β, Snail/Slug, and Embigin expression, suggesting that the TGF-β signaling cascade, comprising PI3K, GSK3-β, Snail/Slug, and Embigin signals, mediates epithelial to mesenchymal transition (EMT) in pancreatic cancer cells. These findings indicate the involvement of Embigin in EMT in pancreatic cancer progression and suggest Embigin as a putative target for the detection and/or treatment of pancreatic cancer.
authors.affiliation: Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dawoon E
authors.initials: DE
authors.lastname: Jung
authors.affiliation: Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jeong Mi
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chanyang
authors.initials: C
authors.lastname: Kim
authors.affiliation: Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Si Young
authors.initials: SY
authors.lastname: Song
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C069503:EMB protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D016212:Transforming Growth Factor beta
keywords: Embigin; Epithelial to Mesenchymal Transition; Pancreatic ductal adenocarcinoma; monocarboxylate transporter2; transforming growth factor-β