ArticleThe Journal of experimental medicine2024
EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation.
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. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- EML4-ALK in Non-small Cell Lung Cancer: Molecular Mechanisms and Targeted Therapies.Technology in cancer research & treatmentPooled it
- EML4-ALK fusion rewires transcriptomic, miRNA, and CAF-associated programs in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Article
- Article
- Deciphering lung cancer at high resolution: a narrative review of applications of single-cell and spatial transcriptomics sequencing.Translational lung cancer research · 2026Review
- AKAP95 condensates regulate transcription and can be targeted in MLL-fusion driven oncogenesis.Nature communications · 2026Article
- Virtual screening and MD simulation-guided discovery of CDK12-IN-3, a potent ALK inhibitor suppressing neuroblastoma growthFrontiers in chemistry · 2026Article
- Review
- Squamous transformation of EGFR-mutant lung adenocarcinoma after EGFR-TKI therapy: clonal continuity, tissue-based diagnosis, and therapeutic evidence gaps.Frontiers in oncology · 2026Review
- Concurrent PIK3CA mutant promotes cachexia through inflammatory signaling in EGFR mutant lung cancer.Nature communications · 2025Article
- Peripheral blood tumor marker levels can indicate the location of lung cancer metastasis.Oncology letters · 2025Article
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Transcriptomic analysis reveals lung cancer and subtype-specific alternative splicing biomarkers regulated by RNA-binding proteins.Molecular therapy. Nucleic acids · 2025Article
- CellMemory: hierarchical interpretation of out-of-distribution cells using bottlenecked transformer.Genome biology · 2025Article
- Cooperative blockade of FLT3 and ALK synergistically suppresses growth of osteosarcoma.Oncogene · 2025Article
- Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation.Frontiers in immunology · 2025Review
- Global research trends on ALK-TKIs in non-small cell lung cancer: a bibliometric analysis.Frontiers in pharmacology · 2025Article
- Concomitant ALK Fusion and TP53/EGFR Mutation Lead to Adverse Prognostic Outcome.The clinical respiratory journal · 2024Review
- Role and clinical value of serum hsa_tsr011468 in lung adenocarcinoma.Molecular medicine reports · 2024Article
- [High KHSRP expression promotes gastric adenocarcinoma metastasis: the mediating role of the JAK1/STAT3 signaling axis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
Corrections and comments
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Authors and funding
33 authors at 12 institutions in 3 countries.
Funding
Abstract
Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, exhibits strong cancer plasticity. We find that ALK rearrangement is detectable in 5.1-7.5% of human LUAS, and transgenic expression of EML4-ALK drives lung adenocarcinoma (LUAD) formation initially and squamous transition at late stage. We identify club cells as the main cell-of-origin for squamous transition. Through recapitulating lineage transition in organoid system, we identify JAK-STAT signaling, activated by EML4-ALK phase separation, significantly promotes squamous transition. Integrative study with scRNA-seq and immunostaining identify a plastic cell subpopulation in ALK-rearranged human LUAD showing squamous biomarker expression. Moreover, those relapsed ALK-rearranged LUAD show notable upregulation of squamous biomarkers. Consistently, mouse squamous tumors or LUAD with squamous signature display certain resistance to ALK inhibitor, which can be overcome by combined JAK1/2 inhibitor treatment. This study uncovers strong plasticity of ALK-rearranged tumors in orchestrating phenotypic transition and drug resistance and proposes a potentially effective therapeutic strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.