ArticleDevelopmental cell2025
FoxA1/2-dependent epigenomic reprogramming drives lineage switching in lung adenocarcinoma.
Article in Developmental cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- HNF4α controls growth, identity, and KRAS inhibitor response in invasive mucinous adenocarcinoma of the lung.The Journal of clinical investigation · 2026Article
- Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026Article
- Bidirectional coupling among EMT, AXL-RB1 signaling and lineage switch drives resistance to osimertinib and worse clinical outcomes in NSCLC.bioRxiv : the preprint server for biology · 2026Article
- CRISPR screen of human pancreatic cancer xenografts identifies a KLF5 proliferation vulnerability through epigenetic modifiers NCAPD2 and MTHFD1.Molecular cancer · 2026Article
- Mechanisms and implications of epithelial cell plasticity in the bladder.Nature reviews. Urology · 2026Review
- FOXA2 in cancer: from fundamental biology to clinical translation.Frontiers in oncology · 2026Review
- Squamous transformation of EGFR-mutant lung adenocarcinoma after EGFR-TKI therapy: clonal continuity, tissue-based diagnosis, and therapeutic evidence gaps.Frontiers in oncology · 2026Review
- Physicochemical features of intrinsically disordered regions predict DNA-demethylation-promoting activity of transcription factors.Epigenetics & chromatin · 2025Article
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- Opposing lineage specifiers induce a protumor hybrid identity state in lung adenocarcinoma.Genes & development · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
The ability of cancer cells to undergo identity changes (i.e., lineage plasticity) plays a key role in tumor progression and response to therapy. Loss of the pulmonary lineage specifier NKX2-1 in KRAS-driven lung adenocarcinoma (LUAD) enhances tumor progression and causes a FoxA1/2-dependent pulmonary-to-gastric lineage switch. However, the mechanisms by which FoxA1/2 activate a latent gastric identity in the lung remain largely unknown. Here, we show that FoxA1/2 reprogram the epigenetic landscape of gastric-specific genes after NKX2-1 loss in mouse models by facilitating ten-eleven translocation (TET)2/3 recruitment, DNA demethylation, histone 3 lysine 27 acetylation (H3K27ac) deposition, and three-dimensional (3D) chromatin interactions. FoxA1/2-mediated DNA methylation changes are highly conserved in human endodermal development and in progression of human lung and pancreatic neoplasia. Furthermore, oncogenic signaling is required for specific elements of FoxA1/2-dependent epigenetic reprogramming. This work demonstrates the role of FoxA1/2 in rewiring the DNA methylation and 3D chromatin landscape of NKX2-1-negative LUAD to drive cancer cell lineage switching.
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