ArticleEMBO reports2021
Phase-separated foci of EML4-ALK facilitate signalling and depend upon an active kinase conformation.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- A meta-analysis of the impact of different ALK variants on targeted therapy efficacy in advanced non-small cell lung cancer.Frontiers in oncology · 2026Pooled it
- Proteomic investigation of signaling dynamics: from static maps to network rewiring.Bioscience reports · 2026Review
- Fusion protein condensate formation via coiled-coil domains.Protein science : a publication of the Protein Society · 2026Article
- Redirecting TRIM21 with TRIMTACs for the targeted degradation of multimeric proteins.The FEBS journal · 2026Review
- Kinase condensates enrich ATP and trigger autophosphorylation.Cell reports · 2026Article
- The oncogenic CCDC6-RET fusion protein is a dual ATP- and ADP-dependent kinase.Nature communications · 2026Article
- Article
- Targeting biomolecular condensates: beyond dissolution.BMC biology · 2026Review
- NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3.Scientific reports · 2026Article
- EML4-ALK Variant-Specific Genetic Interactions Shape Lung Tumorigenesis.Cancer discovery · 2026Article
- Low-order assemblies drive oncogenic RTK fusion signaling without condensation.bioRxiv : the preprint server for biology · 2025Article
- Phase-separating fusion proteins drive cancer by upsetting transcription regulation.Genome biology · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Article
- Computationally designed sensors detect endogenous Ras activity and signaling effectors at subcellular resolution.Nature biotechnology · 2024Article
- Article
- CaMKII suppresses proteotoxicity by phosphorylating BAG3 in response to proteasomal dysfunction.EMBO reports · 2024Article
- Antitumor activity of anlotinib in malignant melanoma: modulation of angiogenesis and vasculogenic mimicry.Archives of dermatological research · 2024Article
- EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation.The Journal of experimental medicine · 2024Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Variants of the oncogenic EML4-ALK fusion protein contain a similar region of ALK encompassing the kinase domain, but different portions of EML4. Here, we show that EML4-ALK V1 and V3 proteins form cytoplasmic foci that contain components of the MAPK, PLCγ and PI3K signalling pathways. The ALK inhibitors ceritinib and lorlatinib dissolve these foci and EML4-ALK V3 but not V1 protein re-localises to microtubules, an effect recapitulated in a catalytically inactive EML4-ALK mutant. Mutations that promote a constitutively active ALK stabilise the cytoplasmic foci even in the presence of these inhibitors. In contrast, the inhibitor alectinib increases foci formation of both wild-type and catalytically inactive EML4-ALK V3 proteins, but not a Lys-Glu salt bridge mutant. We propose that EML4-ALK foci formation occurs as a result of transient association of stable EML4-ALK trimers mediated through an active conformation of the ALK kinase domain. Our results demonstrate the formation of EML4-ALK cytoplasmic foci that orchestrate oncogenic signalling and reveal that their assembly depends upon the conformational state of the catalytic domain and can be differentially modulated by structurally divergent ALK inhibitors.
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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.