Fig. 8. The DAXX SIM2 peptide disrupts the DAXX–SREBP interactions and suppresses tumor growth in vivo.

a MDA-MB-231 cell extracts were subjected to anti-DAXX IP in the absence (0) or the presence of SIM2 (1 and 5 µM). The immunoprecipitates and input were analyzed by immunoblotting. b The MDA-MB-231 cells were implanted into mammary fat pads of female NSG mice (n = 6 tumor-bearing mice). Mice were dosed i.p. daily weekdays for three weeks with vehicle or SIM2 (25 mg kg^–1). Longitudinal tumor volumes, mouse body weights, endpoint tumor weights, and images are shown. c The mouse mammary tumor 4T1 cells were injected into mammary fat pads of female BALB/c mice (n = 6 tumor-bearing mice). Mice were dosed as in (b). Longitudinal tumor volumes, mouse body weights, endpoint tumor weights, and tumor images are shown. d SIM2 dosing reduced the expression of DAXX, SREBP2 and FASN in tumors. Protein extracts from three representative MDA-MB-231 xenograft tumors in vehicle and SIM2-treated mice were subjected to immunoblotting. HSP60 was detected as a loading control. e Lipid profiles of MDA-MB-231 xenograft tumors treated with vehicle or SIM2. Shown are a plot of a principal component analysis of lipid molecules detected by LC/MS, a heatmap of top lipid species, and bar graphs of relative abundance of the indicated lipid molecules. Gray and red bars represent tumor samples from mice treated with vehicle or SIM2, respectively. b, c, e Data are presented as mean values ± SEM and the P values were calculated based on unpaired two-tailed t test, *P < 0.05; **P < 0.01; ***P < 0.001. V vehicle. f A model explaining the antitumor effects of SIM2, which acts to interfere with the interactions between DAXX and SREBP1/2, thereby inhibiting lipogenesis and tumor growth. Source data are provided as a Source Data file.