Extended Data Fig. 12: Impact of DHCR7 loss in vivo.

a, Immunoblot for DHCR7 in MM1S cells DHCR7-proficient and deficient. Representative of n = 2. b, Dose-dependent toxicity of ML210 in DHCR7^WT or DHCR7^KO in the presence of indicated treatments. c, Tumour growth upon implantation of MM1S DHCR7^WT (n = 10) or DHCR7^KO (n = 10). Data are mean ± SEM; p value n.s., Mann–Whitney test one-tailed. In each box, horizontal lines denote mean values, while the box contains the 25th to 75th percentiles of dataset and whiskers mark the 5th and 95th percentiles. d, Representative luminescence images of mice from c. e, Schematic of tail vein injection of DHCR7^WT (n = 5) or DHCR7^KO (n = 5) BL41 cell in mice under selenium-adequate or -deprived diet. f, Immunoblot for GPX4 from tissues of animals related to e. g, Kaplan–Meier plot displaying tumour-free survival (TFS) for mice injected with DHCR7^WT (n = 5) or DHCR7^KO (n = 5) BL41 cells. Data represent the mean ± s.e.m.; Mann–Whitney test one-tailed; A Log-rank (Mantel–Cox) test was conducted for statistical analysis, p values are indicated. h, Luminescence images related to g. i, Immunoblot for DHCR7 in SK-N-DZ DHCR7^KO and DHCR7^WT. j, Relative quantification of cholesterol and 7-DHC levels in SK-N-DZ cells treated with RB38 and Tasin-1. Data are the mean ± s.d. of n = 3 wells from one representative experiment. k, Dose-dependent toxicity of ML210 in the indicated cells. l, Flow cytometry analysis of BODIPY 581/591 C11 oxidation in SK-N-DZ cells induced by RSL3 treatment ([100 nM], 3 h) and Lip1 500 nM. m, Schematic representation illustrates an orthotopic mouse model created by transplanting DHCR7^WT or DHCR7^KO SK-N-DZ cells into the right adrenal gland of NSG mice. n, Kaplan- Meier plot displaying TFS for mice injected orthotopically with DHCR7^WT (blue, n = 6) or DHCR7^KO (red, n = 9) SK-N-DZ cells; *p < 0.05, A Log-rank (Mantel–Cox) test was conducted for statistical analysis. o, Lung colonization was evaluated (left panel) in mice orthotopically transplanted with SK-N-DZ neuroblastoma cells, with DHCR7^WT (red, n = 6) or DHCR7^KO (blue, n = 9), using ex vivo lung bioluminescence analysis (right panel);. p, Representative examples of evidence of metastases from o (indicated by green circle lines), determined by Hematoxylin and Eosin staining from samples of n. Scale bar: 500 µM. Cell viabilities were assessed after 72 h using Alamar blue, data are mean ± s.d. of n = 3 replicates from one representative of three independent experiments (b, k). RB38 (500 nM) and Tasin-1 (500 nM) (b, j, k). Panels created with BioRender.com (e, m).

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