GCLM lactylation mediated by ACAT2 promotes ferroptosis resistance in KRASG12D-mutant cancer. (PubMed, Cell Rep) - Jun 12, 2025 - "Here, we construct wild-type KRAS (KRASWT) and KRASG12D-mutant cancer cells and demonstrate that G12D-mutant cells exhibit increased viability and reduced ferroptosis upon RSL3 or erastin treatment. Importantly, ACAT2 depletion overcomes ferroptosis resistance in KRASG12D-mutant tumors in vivo. Our findings reveal a KRASG12D-driven metabolic adaptation linking GCLM lactylation to ferroptosis resistance, proposing ACAT2 inhibition as a therapeutic strategy for KRAS-mutant cancers."
Journal • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • LDHA
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Baohua Hou; Chuanzhao Zhang; Jiayu Yang; Jike Fang; Jinwei Cui; Qian Yan; Shanzhou Huang; Shiye Ruan; Siyang Liu; Yubin Chen; Zhenchong Li; Zhongyan Zhang
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