ArticleThe Journal of experimental medicine2024
TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026Review
- Transcriptional intermediary factor 1 gamma-based multitarget gene therapeutic strategy for triple-negative breast cancer.Signal transduction and targeted therapy · 2026Article
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- KMT2D loss drives adeno-to-squamous transition and sensitizes TKI-resistant lung cancer to AURKA inhibition.Cell death and differentiation · 2026Article
- Chemokine-chemokine receptor axis: Emerging immunotherapeutic paradigms for solid tumor microenvironment reprogramming.Chinese medical journal · 2026Review
- Coordinated DNA methyltransferase 3A and methyltransferase-like 7A activity reprograms the tumor microenvironment through discoidin domain receptor 1 signaling.Cancer biology & medicine · 2026Article
- TET2: a critical regulatory hub with broad therapeutic implications across human diseases.Frontiers in immunology · 2026Review
- Mitochondrial metabolic-transcriptional axis drives adaptive drug tolerance across major lung cancer subtypes.Frontiers in genetics · 2026Review
- TET knockout cells transit between pluripotent states and exhibit precocious germline entry.The EMBO journal · 2025Article
- IL33-induced lipid droplet formation in mature low-density neutrophils drives colorectal cancer liver metastasis.Cellular & molecular immunology · 2025Article
- Necrotic and apoptotic adipocytes in the hypoxic tumor microenvironment supply triglycerides to induce cisplatin resistance in the metastatic lymph nodes of head and neck carcinoma.Cell death & disease · 2025Article
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment.Biomedicines · 2025Review
- Effect of neutrophils on tumor immunity and immunotherapy resistance with underlying mechanisms.Cancer communications (London, England) · 2025Review
- Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation.Frontiers in immunology · 2025Review
- Mechanism exploration and model construction for small cell transformation in EGFR-mutant lung adenocarcinomas.Signal transduction and targeted therapy · 2024Article
- The Mechanism of Action of the Active Ingredients ofViruses · 2024Article
- Methionine Restriction Reduces Lung Cancer Progression and Increases Chemotherapy Response.bioRxiv : the preprint server for biology · 2024Article
- Causal association between skin cancer and immune cells: mendelian randomization (MR) study.BMC cancer · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
23 authors.
Funding
Abstract
Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.
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