ACSS2/AATF Drives Soluble FasL-Mediated CD8⁺ T Cell Apoptosis in Pancreatic Neuroendocrine Tumors.

ABSTRACT: Besides the traditional carbon sources, Acetyl coenzyme A has recently been shown to be generated from acetate in various cancers, which subsequently promotes tumor growth and immune escape. However, the mechanism of Acetyl coenzyme A availability in pancreatic neuroendocrine tumors (PNETs) remains largely unknown. Herein, the metabolic-epigenetic modification driven by acetyl coenzyme A synthase 2 (ACSS2) and its effect on the Fas/FasL system in PNETs is investigated. ACSS2 is highly expressed in PNETs and significantly correlated with patient prognosis. Mechanistically, ACSS2 activity or acetate supplementation induces histone H3/H4 hyperacetylated in PNET cells. This epigenetic modification recruits the transcription factor AATF to co-regulate FasL transcription, specifically enhancing

SUBMITTER: Dang Q 

PROVIDER: S-EPMC12561415 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature