Fig. 6
From: O-GlcNAcylation mediates metastasis of cholangiocarcinoma through FOXO3 and MAN1A1
O-GlcNAcylation regulated activations of Akt and Erk and expression of FOXO3 and MAN1A1. OGT was suppressed in parental (KKU-213 and KKU-214) and highly metastatic (KKU-213L5 and KKU-214L5) CCA cells using siOGT. a siOGT treatment inactivated the phosphorylation of Akt and Erk but not Ikk. b The modulations of Akt and Erk on FOXO3 expression were revealed using Akt and Erk inhibitors. CCA cells were treated with various concentrations of Akt inhibitor, MK-2206 and (c) Erk inhibitor, PD98059, for 24 h. The expression of pAkt/Akt, pErk/Erk, phospho-FOXO3, FOXO3 and MAN1A1 were determined using western blotting. d The MK-2206-treated L5 CCA cells were incubated with 20 µM of cycloheximide (CHX) for 1, 3, and 6 h. FOXO3 levels at each time point were determined using western blotting and compared with those of the untreated control cells. The data are represented as the mean ± SD from three independent experiments. Inhibition of Akt activation significantly reduced (e) migration and (f) invasion abilities of CCA cells and these effects could be rescued by kifunensine (Kif) treatment. The results are mean ± SEM of one representative from two independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001, student’s t test
