Fig. 1: Inhibition of major anabolic synthesis routes differentially impacts the motility potential of cancer cells. | Nature Communications

Fig. 1: Inhibition of major anabolic synthesis routes differentially impacts the motility potential of cancer cells.

From: Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cancer cell migration and metastasis

Fig. 1

a Synthesis routes of metabolic building blocks (lipids, nucleotides, and proteins) and pharmacologic intervention points of the selected drug panel. b MDA-MB-468 cells were counted after 48 h treatment with 100 nM Sirolimus (SIR) (n = 3), 1 μM Simvastatin (SIM) (n = 3), 50 nM Rotenone (Rot) (n = 5), galactose (Gal) (n = 5) supplementation, 50 nM Methotrexate (MTX) (n = 4), 1 μM Pemetrexed (PEM) (n = 4), 0.5 mM hydroxyurea (HU) (n = 4), and 100 nM Clofarabine (CLO) (n = 4). Mean ± SD; ordinary one-way ANOVA with Dunnett’s multiple comparisons test. Unlabeled comparisons to Ctrl are all significant with p < 0.0001. c MDA-MB-468 cells were treated as in (b). Cell death was assessed by flow cytometry and AnnexinV-FITC/PI-staining; mean ± SD of independent experiments (n = 8 (Ctrl), n = 4 (SIR, SIM, PEM, CLO), n = 3 (Rot, Gal, MTX, HU)). Two-way ANOVA with Dunnett’s multiple comparisons test. d, e Migration of MDA-MB-468 cells upon (d) 50 nM Rot (n = 5), Gal (n = 5), 1 μM SIM (n = 3), and 100 nM SIR (n = 4) or (e) 50 nM MTX (n = 7), 1 μM PEM (n = 3), 0.5 mM HU (n = 4), and 100 nM CLO (n = 4) and respective area under curve (AUC); mean ± SEM of independent experiments; Brown-Forsythe and Welch one-way ANOVA with Dunnett’s multiple comparisons test. f, g Correlation of cell migration (AUC over 40 h, mean ± SEM, (n = as in (d, e)) and proliferation (fold cell growth after 48 h, mean ± SD (n = as in (b)). MDA-MB-468 cells were treated as in (b) and (d, e). h Migration and invasion of MDA-MB-468 cells treated for 24 h with 50 nM MTX using non-coated (migration) or ECM-Collagen-coated (invasion) Boyden chambers. Mean ± SEM (Migration: n = 3, Invasion: n = 7 (Ctrl), 5 (MTX, 3 (Pem)); Brown-Forsythe and Welch one-way ANOVA with Dunnett’s multiple comparisons test. i Proliferation of MTX-resistant MDA-MB-468 cells upon the indicated concentrations of MTX [nM]; mean ± SEM of independent experiments (n = 4). j Migration of parental and MTX-resistant MDA-MB-468 cells and respective AUC; mean ± SEM of independent experiments (parental n = 15, resistant n = 6); unpaired, two-tailed t-test with Welch’s correction. Time point of 50% wound closure is indicated. Source data are provided as a Source Data file.

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