Fig. 7: Mitochondrial CD147 promotes lactate-induced stemness potentials in detached breast cancer cells. | Nature Communications

Fig. 7: Mitochondrial CD147 promotes lactate-induced stemness potentials in detached breast cancer cells.

From: Lactate mitochondrial oxidation drives stemness potential in metastatic breast cancer

Fig. 7: Mitochondrial CD147 promotes lactate-induced stemness potentials in detached breast cancer cells.The alternative text for this image may have been generated using AI.

A, B Typical peak maps of 2-2H-lactate metabolic flux analysis (A) and 2H-labeled M + 1 metabolites (B, n = 3 biologically independent samples). WT, wild type; KO, CD147 knockout; mito147, mitochondrial CD147-expression; mito147 + scFv, mito147 cells+anti-mitochondrial CD147 scFv (single-chain variable fragment). C Lactate (Lac) levels in supernatants of AR MCF7/T47D WT/KO/mito147 cells (n = 3 independent experiments). ****P < 0.0001, one-way ANOVA with Bonferroni correction. D, E OCRs (D), ALDH+ ratios (E, left), and tumorsphere numbers (E, right) in AR MCF7/T47D WT/KO/mito147 cells (n = 3 independent experiments). E left, *P = 0.023, 0.0118 (MCF7, T47D), **P = 0.0011, ***P = 0.0003; E right, **P = 0.0033, ***P = 0.0003, ****P < 0.0001, one-way ANOVA with Bonferroni correction. F Tumor growth curves of MCF7 WT/KO/mito147 cell-bearing mice (n = 5 mice/group) with 800 mg/kg lactate administration. WT vs KO, **P = 0.0044, ****P < 0.0001; mito147 vs KO, & &P = 0.0087, 0.0012 (12, 15 day), & & & &P < 0.0001; two-way ANOVA with Bonferroni correction. G–I Lung nodule (G, n = 10 mice/group), ALDH+ and CD44highCD24−/low ratios (H, n = 5 mice/group), and SOX2/MCT1/LDHB protein levels (I, n = 4 mice/group, α-Tubulin, loading control) in tumors from indicated cell-bearing mice with 800 mg/kg lactate administration. **P = 0.0056, ****P < 0.0001, one-way ANOVA with Bonferroni correction. J, K Plasma CTCs numbers (J, n = 10 mice/group) in 800 mg/kg lactate-administered indicated cell-bearing mice, and SOX2 immunofluorescence intensity (K; WT, n = 120 cells from 6 mice; KO, n = 67 cells from 5 mice; mito147, n = 142 cells from 6 mice) in CTCs. ***P = 0.0001, ****P < 0.0001, one-way ANOVA with Bonferroni correction. CTC circulating tumor cell. L DNMT3B protein levels in MCF7/T47D WT/KO/mito147 cells as indicated. Representative of 3 independent experiments. α-Tubulin, loading control. DNMT3B DNA methyltransferase 3 beta. Data are mean ± SEM. Source data are provided as a Source Data file.

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