Embigin is overexpressed in pancreatic ductal adenocarcinoma and regulates cell motility through epithelial to mesenchymal transition via the TGF-β pathway.

Abstract

Embiginis a member of the immunoglobulin superfamily and encodes a transmembrane glycoprotein. There have been reports ofEmbigininvolvement in neuromuscular junction formation and plasticity; however, the molecular functions ofEmbiginin other organs are unknown. Our aim was to investigate the possible role ofEmbigininpancreaticcancer. Inpancreaticductaladenocarcinomatissues,Embiginexpression was higher than that in normalpancreatictissues. Immunohistochemical analysis revealed expression ofEmbigininpancreaticcancer cells, as well as expression of monocarboxylate transporter 2 (MCT2) in cancer tissues. To gain further insight, we transfected BxPC-3 and HPACpancreaticcancer cells with siRNA or shRNA targetingEmbiginand observed reductions incellproliferation, migration, invasion, wound healing, and reduced levels of matrix metalloproteinases-2 and -9. Silencing ofEmbiginincreased intracellular L-lactate concentration by 1.5-fold and decreased MCT2 levels at the plasma membrane. Furthermore,Embiginsilencing 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, andEmbiginexpression, suggesting that the TGF-β signaling cascade, comprising PI3K, GSK3-β, Snail/Slug, andEmbiginsignals, mediatesepithelialtomesenchymaltransition(EMT) inpancreaticcancer cells. These findings indicate the involvement ofEmbiginin EMT inpancreaticcancer progression and suggestEmbiginas a putative target for the detection and/or treatment ofpancreaticcancer.