Journal: Nature

Article Title: ACLY inhibition promotes tumour immunity and suppresses liver cancer

doi: 10.1038/s41586-025-09297-0

Figure Lengend Snippet: a , Graphical representation showing metabolic enzymes in the regulation of sterol and fatty acid synthesis. The graphical representation was created using BioRender ( https://biorender.com ). ( b-c ), Effect of BA (Bempedoic acid) and EVT0185 on b , lactate and c , acetate incorporation into fatty acids and sterols in WT and Acly KO mouse hepatocytes. Each stacked bar represents the mean ± SEM, % suppression with BA or EVT0185 in WT (n = 3 ) and Acly KO (n = 3) mice. ( d-g ) Inhibitory effect of EVT0185-CoA on the activity of d , AMPK; e , ACC1; f , ACC2; and g , ACSS2. Each line graph represents the mean ± SEM, enzyme activity inhibition by EVT0185-CoA (n = 3 samples/group). ( h and i ) Effect of Bempedoic acid and EVT0185 on clonogenic survival/colony formation in h , Hep3B human, and i , Hepa1-6 mouse HCC cell lines. Each line graph represents the mean ± SEM colony formation in cells treated with EVT0185 or Bempedoic acid (n = 4 biologically independent samples/treatment groups).

Article Snippet: Recombinant protein of human ACSS2, transcript variant 1 (accession no. NM_018677 ) tagged with MYC–DDK was obtained from Origene (TP304260).

Techniques: Activity Assay, Inhibition

Journal: Nature

Article Title: ACLY inhibition promotes tumour immunity and suppresses liver cancer

doi: 10.1038/s41586-025-09297-0

Figure Lengend Snippet: a , Differential expression analysis comparing MASH-HCC (n = 53) and non-tumor adjacent liver (n = 29), MASH liver (n = 74), cirrhotic liver (n = 8), and healthy liver tissue (n = 6); two-tailed t-test; 5% FDR as implemented in limma. b , Overlap between significantly upregulated and downregulated genes in each pairwise comparison. c , Gene expression of lipogenic enzymes acetyl-CoA carboxylase ( ACACA or ACACB ), ACSS2 , and FASN across disease states (MASH-HCC, n = 53; non-tumor adjacent, n = 29; MASH liver, n = 74; cirrhotic liver, n = 8; healthy liver, n = 6). Boxplot lines represent the first quartile, median, and third quartile. Whiskers connect the minimum and maximum values. d , ACLY upregulation in human MASH-HCC compared to all other tissue types using scRNAseq samples. Significance assessed using Wilcoxon rank-sum tests comparing each condition to MASH-HCC, with p-values adjusted using the Benjamini-Hochberg method. Exact p-adj values: vs healthy P adj = 6.9 × 10 −247 , vs MALSD P adj = 1.0 × 10 −16 , vs non-tumor adjacent P adj = 1.6 × 10 −18 . e , Differential expression analysis of genes associated with ACLY expression in MASH-HCC; two-tailed t-test; 5% FDR as implemented in limma. f , Principal component embeddings of genes differentially expressed with respect to ACLY expression validate stratification of MASH-HCC tissues by high, medium, and low ACLY expression levels. g , Upregulation of CXCL13 among human MASH-HCC samples with reduced (bottom tertile, n = 18) relative to elevated (top tertile, n = 18) ACLY expression. Significance determined by two-tailed t-test with a false discovery adjusted threshold of 5% as implemented in limma. Boxplot lines represent the first quartile, median, and third quartile. Whiskers connect the minimum and maximum values. h , Identification of co-expression modules associated with ACLY expression and immune features. i , Significant biological processes associated with the immune and ACLY associated gene co-expression module.

Article Snippet: Recombinant protein of human ACSS2, transcript variant 1 (accession no. NM_018677 ) tagged with MYC–DDK was obtained from Origene (TP304260).

Techniques: Quantitative Proteomics, Two Tailed Test, Comparison, Gene Expression, Expressing