Fig. 5

GAA metabolism promotes HMGA-induced EMT via upregulated MYC expression. A-B GSEA (left) and GSVA (right) results of the hallmark pathways based on DEGs between PANC-1-IN-Lv-Con and PANC-1-IN-Lv-sh-GATM. C GSEA result of MYC target pathway based on DEGs. D RT-qPCR showing the expression of Myc, Notch and E2f after GATM knockdown. E Identification of transcription factor proteins family based on differentially expressed transcription factor genes. F Western blot showing HMGA1 and HMGA2 expression after GATM knockdown. G-H Migration ability analysis and western blot showing EMT marker proteins expression of pancreatic cancer cells after GATM knockdown and HMGA1/2 overexpression. I-J Western blot showing the expression of c-Myc, HMGA1, HMGA2, and ERK/p-ERK in pancreatic cancer cells after intervention of GAA metabolism. K CUT&RUN analysis showing levels of c-Myc enriched to Hmga1 and Hmga2 promoters. L Luciferase reporter gene assay showing c-Myc protein targeting the promoter of Hmga1 and Hmga2. M–N Western blot showing the expression of c-Myc-HMGA-E-cadherin in PANC-1-IN cells. O-P RT-qPCR showing the expression of Myc, Hmga1 and Hmga2 in xenograft tumors. Data in (G, L) and (D, O,-P) are presented as mean ± SEM by ordinary one-way ANOVA (Tukey’s multiple comparisons test) and unpaired t test respectively. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001