Fig. 7.
Caspase-10 downregulates ACLY-promoted aggressive tumor phenotype a A549Luc2 control (control), caspase-10 knockdown (CASP10kd), caspase-10/ACLY double knockdown (CASP10kd/ACLYkd), and caspase-10/GCN5 double knockdown (CASP10kd/GCN5kd) cells were orthotopically injected into the lung of nude mice. Post-one week of injection, mice were administered metformin (5 mg/ml in drinking water). Bioluminescence imaging was performed weekly and representative images are shown. The data shown are representative of three independent experiments using five individual mice per group. b Bioluminescence quantification (panel a above) was performed at indicated time points. The data shown are representative of three independent experiments using five individual mice per group. Error bars are mean ± SD from five individual mice (n = 5 mice per group). Statistical analyses were done using two-way ANOVA (Tukey’s post hoc test). ***P < 0.001. c At the end of 4 weeks, blood from mice in (panel a above), was used to isolate genomic DNA for examining circulating tumor cells. The data shown are representative of three independent experiments using five individual mice per group. Error bars are mean ± SD from five individual mice (n = 5 mice per group). Statistical analyses were done using one-way ANOVA (Tukey’s post hoc test). ***P < 0.001. d At the end of 5 weeks, tumor lysates were prepared (panel a above) and analyzed by immunoblotting for the indicated proteins. The data shown are representative of three independent experiments using five individual mice per group. e Representative image of immunostaining of ACLY, caspase-10 and H3K9Ac in different grades of human lung adenocarcinoma and matched normal adjacent tissue (NAT). DAPI was used to counter stain nucleus. Scale bar: 20 μm. f Quantitation of ACLY, caspase-10 and H3K9Ac levels in different grades of human lung adenocarcinoma with respect to matched normal adjacent tissue. The data shown are representative of three independent experiments. Error bars are mean ± SD. Statistical analyses were done using one-way ANOVA (Dunn’s multiple comparison test). *P < 0.05, ***P < 0.001. Source data are provided as a Source Data file