ArticleCell discovery2021
Phase separation of EML4-ALK in firing downstream signaling and promoting lung tumorigenesis.
Article in Cell discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- EML4-ALK in Non-small Cell Lung Cancer: Molecular Mechanisms and Targeted Therapies.Technology in cancer research & treatmentPooled it
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Eugenol as a game-changer: overcoming osimertinib resistance in non-small cell lung cancer by inhibiting glycolysis via the tripartite motif containing 59/extracellular signal-regulated kinase pathway.Anti-cancer drugs · 2026Article
- Small molecules modulate the biomolecular condensates and liquid‒liquid phase separation.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer.Cell communication and signaling : CCS · 2026Review
- A Unique Chimeric RNA: ERCC1-iASPP Drives Benzo[a]pyrene-Induced Lung Carcinogenesis via Dual Coding and Non-Coding Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3.Scientific reports · 2026Article
- Development and validation of a diagnostic machine learning model for gastric cancer risk based on double-negative T cell-related features.Cancer cell international · 2026Article
- AKAP95 condensates regulate transcription and can be targeted in MLL-fusion driven oncogenesis.Nature communications · 2026Article
- Lung cancer organoids for functional precision oncology: from disease modeling to clinical decision support.Frontiers in oncology · 2026Review
- Phase separation of p85β modulates hepatocellular carcinoma progression through POLR1A.International journal of biological sciences · 2026Article
- Low-order assemblies drive oncogenic RTK fusion signaling without condensation.bioRxiv : the preprint server for biology · 2025Article
- Biomolecular condensates in lung cancer: from molecular mechanisms to therapeutic targeting.Cell death discovery · 2025Review
- Phase-separating fusion proteins drive cancer by upsetting transcription regulation.Genome biology · 2025Article
- Synthetic ZFTA fusions pinpoint disordered protein domain acquisition as a mechanism of brain tumorigenesis.Nature cell biology · 2025Article
- Pan-Cancer Analysis of Oncogenic MET Fusions Reveals Distinct Pathogenomic Subsets with Differential Sensitivity to MET-Targeted Therapy.Cancer discovery · 2025Article
- Article
- Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation.Frontiers in immunology · 2025Review
- Liquid-liquid phase separation: an emerging perspective on the tumorigenesis, progression, and treatment of tumors.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EML4-ALK fusion, observed in about 3%-7% of human lung adenocarcinoma, is one of the most important oncogenic drivers in initiating lung tumorigenesis. However, it still remains largely unknown about how EML4-ALK fusion exactly fires downstream signaling and drives lung cancer formation. We here find that EML4-ALK variant 1 (exon 1-13 of EML4 fused to exon 20-29 of ALK) forms condensates via phase separation in the cytoplasm of various human cancer cell lines. Using two genetically engineered mouse models (GEMMs), we find that EML4-ALK variant 1 can drive lung tumorigenesis and these murine tumors, as well as primary tumor-derived organoids, clearly show the condensates of EML4-ALK protein, further supporting the findings from in vitro study. Mutation of multiple aromatic residues in EML4 region significantly impairs the phase separation of EML4-ALK and dampens the activation of the downstream signaling pathways, especially the STAT3 phosphorylation. Importantly, it also significantly decreases cancer malignant transformation and tumor formation. These data together highlight an important role of phase separation in orchestrating EML4-ALK signaling and promoting tumorigenesis, which might provide new clues for the development of clinical therapeutic strategies in treating lung cancer patients with the EML4-ALK fusion.
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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.