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Fig. 8 | Journal of Experimental & Clinical Cancer Research

Fig. 8

From: O-GlcNAcylation homeostasis controlled by calcium influx channels regulates multiple myeloma dissemination

Fig. 8

Hyper-O-GlcNAcylation promotes ubiquitin-mediated proteasomal degradation of ITGA4 and ITGB7. a RPMI8226 cells were pretreated with the proteasome inhibitor MG-132 (50 μM) for 3 h, followed by thiamet G (10 μM) treatment for 6 h, and ITGA4 and ITGB7 levels were analyzed by Western blotting. (lower) Quantitative analysis of ITGA4 (left) and ITGB7 (right) levels, normalized to β-actin and relative to non-treated cells (NTX). Data mean ± SD (n = 4). *P < 0.05, ***P < 0.001 versus NTX cells or thiamet G-treated cells alone; one-way ANOVA with Tukey’s multiple comparison test. ns, not significant. b RPMI8226 cells were pretreated with MG-132 to prevent proteasomal degradation and then treated with thiamet G (10 μM) for 6 h. The cells were then subjected to immunoprecipitation (IP) with anti-ITGA4 and anti-ITGB7 antibodies, and the immune complexes were detected for O-GlcNAcylation or ubiquitination by Western blotting. IP inputs were also evaluated for ITGA4, ITGB7 or β-actin for comparison. c A schematic illustration for the regulation of MM cell motility and dissemination by Ca2+ influx/O-GlcNAc axis. Ca2+ influx channels, including TRPM7, ORAI1, and STIM1, regulate Ca2+ entry in MM cells. Following Ca2+ influx channels inhibition, cellular O-GlcNAcylation is elevated and activates ITGA4 and ITGB7. O-GlcNAcylation of ITGA4 and ITGB7 induces downregulation of the two adhesion proteins via ubiquitin (Ub)-proteasomal degradation, causing a repression of MM cell motility and dissemination

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