Fig. 2: Loss of KMT2D promotes HNSCC growth and upregulates glycolysis. | Nature Communications

Fig. 2: Loss of KMT2D promotes HNSCC growth and upregulates glycolysis.

From: Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma

Fig. 2

a Protein levels of KMT2D and H3K4me1 in KMT2D-WT and KMT2D-KO SCC23 cells by western blot. n  =  3 independent experiments. b, c Xenografted tumor growth (b) and weight (c) of KMT2D-WT and KMT2D-KO SCC23 cells in nude mice. Values are mean ± SD. n = 6:6. **p < 0.01 by two-way ANOVA with Bonferroni correction (b). *p < 0.05 by unpaired two-tailed Student’s t test (c). d–g Enrichment plots of gene sets for glycolysis (d), mTORC1 signaling (e), MYC targets (f), and Ribosome biogenesis (g) identified by GSEA between KMT2D-KO and KMT2D-WT SCC23 cells. h Heatmap of glycolytic genes from KMT2D-WT and KMT2D-KO SCC23 cells by RNA-seq from 2 independent experiments. i mRNA levels of glycolytic genes from KMT2D-WT and KMT2D-KO SCC23 cells by qRT-PCR. Values are mean ± SD from three independent experiments. **p < 0.01 by one-way ANOVA. j Protein levels of LDHB and PGK1 in KMT2D-WT and KMT2D-KO SCC23 cells by western blot. n  =  3 independent experiments. k Glucose uptake in KMT2D-WT and KMT2D-KO SCC23 cells. Values are mean ± SD from three independent experiments. **p < 0.01 by one-way ANOVA. l Lactate excretion from KMT2D-WT and KMT2D-KO SCC23 cells. Values are mean ± SD from three independent experiments. **p < 0.01 by one-way ANOVA. m,n Intracellular levels of 2-PG (m) and pyruvate (n) in KMT2D-WT and KMT2D-KO SCC23 cells. Values are mean ± SD from three independent experiments. **p < 0.01 by one-way ANOVA. o, p IHC staining and quantification of LDHB (o) and PGK1 (p) in Kmt2d-WT and Kmt2d-HT mouse HNSCC. Scale bar, 50 µm. Values are mean ± SD. n = 8:8. **p < 0.01 by unpaired two-tailed Student’s t test. Source data are provided as a Source Data file.

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