Fig. 4: KMT2D-deficient HNSCC is hypersensitive to DNA cross-linking agents upon glycolytic inhibition. | Nature Communications

Fig. 4: KMT2D-deficient HNSCC is hypersensitive to DNA cross-linking agents upon glycolytic inhibition.

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

Fig. 4

a Representative scatter plots and quantification of apoptotic KMT2D-WT and KMT2D-KO SCC23 cells treated with 2-DG, MMC, or 2-DG plus MMC. Values are mean ± SD from three independent experiments. **p < 0.01 vs WT in the corresponding treated conditions by unpaired two-tailed Student’s t test. b,c Volume of KMT2D-KO SCC23 (b) and KMT2D-mutant SCC46 (c) orthotopic xenografts treated with 2-DG, MMC, or 2-DG plus MMC in nude mice. Scale bar, 2 mm. Values are mean ± SD. n = 6 per group. *p < 0.05, **p < 0.01 by one-way ANOVA. d,e IF staining (d) and quantification (e) of cleaved Caspase-3 positive cells in SCC46 orthotopic xenografts. Scale bar, 20 µm. Values are mean ± SD. n = 6 per group. **p < 0.01 by one-way ANOVA. f Experimental design for 2-DG and MMC treatment in 4NQO-induced Kmt2d-HT mouse HNSCC. g Representative image of tongue lesions and quantification of lesion areas. Scale bar, 2 mm. Values are mean ± SD. n = 11:12:12:12. **p < 0.01 by one-way ANOVA. h Representative H&E staining of HNSCC and quantification of HNSCC number and area. Scale bar, 200 µm. Values are mean ± SD. n = 11:12:12:12. *p < 0.05, **p < 0.01 by one-way ANOVA. i Quantification of HNSCC invasion grades. *p < 0.05, **p < 0.01 by two-sided Cochran-Armitage test. j IHC staining of PCK positive cells and quantification of the metastatic area in cervical lymph nodes. Scale bar, 200 µm. Values are mean ± SD. n = 11:12:12:12. *p < 0.05, **p < 0.01 by one-way ANOVA. k Quantification of metastatic lymph nodes. **p < 0.01 by two-sided chi-square test. l Volume of KMT2D-KO SCC23 orthotopic xenografts treated with 2-DG, cisplatin, or 2-DG plus cisplatin in nude mice. Scale bar, 2 mm. Values are mean ± SD. n = 8 per group. **p < 0.01 by one-way ANOVA. m Representative IHC staining of PCK positive cells in cervical lymph nodes and quantification of metastatic lymph nodes. Scale bar, 200 µm. n = 8 per group. *p < 0.05, **p < 0.01 by two-sided chi-square test. Source data are provided as a Source Data file.

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