ACSS2 is required for colorectal cancer progression and a druggable target for colorectal cancer treatment
ACSS2 expression is markedly elevated in all stages of human colorectal cancer (CRC), and Acss2 silencing or genetic ablation leads to a marked reduction in CRC tumor load in allograft and xenograft models and CRC models induced by epithelial Apc deletion or azoxymethane/dextran sodium sulfate treatment.
Acyl‑CoA synthetase short‑chain family member 2 (ACSS2) converts acetate to acetyl‑CoA and is markedly up‑regulated in all stages of human colorectal cancer (CRC). Loss of ACSS2 by silencing, genetic ablation, or pharmacological inhibition markedly reduces tumor burden in allograft, xenograft, Apc‑mutant, and azoxymethane/dextran‑sodium‑sulfate (AOM/DSS) mouse models. ACSS2‑deficient tumors show increased DNA damage, apoptosis, and infiltration of macrophages and CD8⁺ T cells. ACSS2 promotes tumor growth by preventing DNA damage‑induced apoptosis under nutritional stress, via nuclear translocation and histone acetylation. Thus, ACSS2 is a potential druggable target for CRC therapy.
Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.
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