ArticleProceedings of the National Academy of Sciences of the United States of America2024
CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Safety, pharmacokinetics and efficacy of HA121-28 in patients with advanced solid tumors and RET fusion-positive non-small-cell lung cancer: a multicenter, open-label, single-arm phase 1/2 trial.Signal transduction and targeted therapy · 2025Trial
- Condensates in fusion oncoprotein-driven leukemia: new biology and therapeutic opportunities.Trends in cancer · 2026Review
- Liquid-Liquid Phase Separation (LLPS) in Tumor Biology: Special Focus on the Process of Transcription.International journal of molecular sciences · 2026Review
- Systematic mapping of chromatin dysregulation driven by viral transcriptional regulators at scale.bioRxiv : the preprint server for biology · 2026Article
- The CDKL5 kinase undergoes liquid-liquid phase separation driven by a serine-rich C-terminal region.Life science alliance · 2026Article
- Low-order assemblies drive oncogenic RTK fusion signaling without condensation.bioRxiv : the preprint server for biology · 2025Article
- Genomic Characterization of Papillary Thyroid Carcinoma: Age Differences in Tumor Aggressiveness and Immune Infiltration.Diagnostics (Basel, Switzerland) · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- Construction and validation of an EGFR-related risk signature identifiedTranslational cancer research · 2025Article
- BYS10, a novel selective RET inhibitor, exhibits potent antitumor activity in preclinical models.Frontiers in pharmacology · 2025Article
- Liquid-liquid phase separation: a new perspective on respiratory diseases.Frontiers in immunology · 2024Review
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13 authors.
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Abstract
Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche is a ternary complex based on the chimeric RET liquid-liquid phase separation. The complex comprises the rearranged kinase (RET fusion); the adaptor (GRB2), and the effector (SHC1). Together, they orchestrate the Ras/MAPK signal cascade, which is dependent on tyrosine kinase. CCDC6-RET fusion undergoes LLPS requiring its kinase domain and its fusion partner. The CCDC6-RET fusion LLPS promotes the autophosphorylation of RET fusion, with enhanced kinase activity, which is necessary for the formation of the signaling niche. Within the signal niche, the interactions among the constituent components are reinforced, and the signal transduction efficiency is amplified. The specific RET fusion-related signal niche elucidates the mechanism of the constitutive activation of the Ras/MAPK signaling pathway. Beyond just focusing on RET fusion itself, exploration of the ternary complex potentially unveils a promising avenue for devising therapeutic strategies aimed at treating RET fusion-driven diseases.
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