Cell Death Discovery, Published online: 26 May 2026; doi:10.1038/s41420-026-03165-0
Activation of methionine metabolism mediated by HNF4Ξ± confers ferroptosis resistance in hepatocellular carcinoma
Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10527-2
A reconstruction method based on Gaussian-apodized single-sideband electron ptychography removes artefacts to enable the high-fidelity identification of guest species in porous materials.
Cell Death Dis. 2026 Apr 14. doi: 10.1038/s41419-026-08712-2. Online ahead of print.
ABSTRACT
Lung adenocarcinoma (LUAD), a leading cause of cancer mortality, involves incompletely understood epigenetic-metabolic crosstalk. We identified ANP32E as a key regulator through multi-omics (TCGA, scRNA-seq) and clinical analyses, finding its overexpression correlates with poor prognosis. Functionally, ANP32E knockdown suppressed proliferation, migration, and glycolysis in LUAD cells (A549/H1975) and attenuated xenograft growth, while overexpression promoted tumorigenesis. Mechanistically, ANP32E transcriptionally upregulates histone demethylase KDM3B, reducing repressive H3K9me2 marks at the EGFR promoter to enhance EGFR transcription. This activates PI3K/AKT signaling, inducing inhibitory GSK3Ξ² phosphorylation. Combined with ANP32E-mediated GSK3Ξ² suppression, this dual inactivation liberates oncogenic glycolysis. Crucially, KDM3B silencing or EGFR inhibition (Cetuximab) abrogated ANP32E-driven phenotypes. High-throughput screening identified Penta-O-galloyl-Ξ²-D-glucose (PGG) as an ANP32E-targeting compound, with molecular dynamics confirming binding. PGG dose-dependently inhibited the ANP32E/KDM3B/EGFR axis in vitro and suppressed tumor growth in vivo. Thus, ANP32E drives LUAD progression via KDM3B/EGFR-mediated GSK3Ξ² inactivation, representing a prognostic biomarker and therapeutic target validated by PGG.
PMID:41980942 | DOI:10.1038/s41419-026-08712-2
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