GFAT1/HBP/O-GlcNAcylation Axis Regulates β-Catenin Activity to Promote Pancreatic Cancer Aggressiveness

Figure 5

β-Catenin mediates the oncogenic roles of GFAT1 in PDAC cells. (a) The effect of GFAT1 knockdown on the β-catenin activity in BxPC3 and SW1990 cells was detected by luciferase TOP/FOP activity experiment. (b) The effect of GFAT1 knockdown on the cyclin D1 and c-Myc mRNA expression was measured by real-time qPCR. (c) Western blotting analysis of the level of O-GlcNAcylation upon OSMI-1 treatment; quantification data was shown, and the β-actin was used as an internal control. (d) The effect of OSMI-1 treatment on β-catenin activity and its downstream targets in BxPC3 and SW1990 cells. (e–g) The effect of GFAT1 knockdown on BxPC3 cell proliferation and invasion upon introduction of β-catenin S33Y mutant plasmid. (h) Activated PI3K/AKT/mTOR signaling promotes GFAT1 expression, which increases the production of UDP-GlcNAc, inducing aberrant stability of β-catenin. Finally, β-catenin promotes tumor growth and metastasis through downstream targets, such as CCND1 and c-Myc. ; .

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