Fig. 3: Chemotherapy-induced HBP activation is regulated by the AKT/XBP-1 axis. | Cell Death & Disease

Fig. 3: Chemotherapy-induced HBP activation is regulated by the AKT/XBP-1 axis.

From: O-GlcNAc elevation through activation of the hexosamine biosynthetic pathway enhances cancer cell chemoresistance

Fig. 3

a AKT has a role in activating XBP1 and GFAT. The indicated cells were treated with DOX (0.1 μM for MCF-7, 1 μM for MCF-7/ADR and SMMC-7721) alone or together with 1 μM MK2206 for 6 h. DMSO was used as a control. The protein levels were examined by immunoblotting. bInduction of UDP-GlcNAc by DOX is attenuated by AKT inhibition. Chromatograms of polar metabolites in MCF-7/ADR and SMMC-7721 cell extracts from control cells (red line), cells treated with 1 μM DOX (blue line) or 1 μM MK2206 (green line) alone and cells treated with DOX plus MK2206 (black line) for 24 h show the regions corresponding to the UDP-GlcNAc derivative, UDP-GalNAc derivative and probenecid retention times. c XBP1 acts upstream of GFAT. The indicated cell lines were transfected with scrambled siRNA (siRNA-Scr) or XBP1 siRNA (siXBP1) for 48 h and then treated with 1 μM DOX. The protein levels after treatment with DOX for 6 h were examined by immunoblotting. The cell viability after treatment with DOX for 24 h was assessed through an MTS assay. d AKT/XBP1 axis regulates GFAT expression in a UPR-independent manner. The indicated cells were treated with 1 μM DOX alone or together with 3 μM VST for 6 h. DMSO was used as a control. The protein levels were examined by immunoblotting. The data represent the means ± SEM, N = 3, *p < 0.05, **p < 0.01

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