ArticleCell discovery2024
Cancer cells sense solid stress to enhance metastasis by CKAP4 phase separation-mediated microtubule branching.
Article in Cell discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Review
- Alterations of actin in aging.Journal of cell science · 2026Review
- Fibronectin 1 mediates pressure-induced aggressive phenotypes in colorectal cancer cells and cancer stem cells.Cancer cell international · 2026Article
- Nuclear Mechanotransduction Across the Metastatic Cascade: Decoding Spatiotemporal Heterogeneity in Cancer Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- LZTS2 Negatively Regulates Centrosomal CEP135 Levels and Microtubule Nucleation.Cytoskeleton (Hoboken, N.J.) · 2026Article
- Phase separation and the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Liquid-Liquid Phase Separation in Major Hallmarks of Cancer.Cell proliferation · 2026Review
- Ultrasound-driven mechanical immunomodulation enhances tumor treatment sensitivity: advances from tumor mechanical immunobiology to immunotherapy applications.Frontiers in immunology · 2026Review
- Harnessing Phase Separation in the Extracellular Matrix: From Mechanisms to Therapeutic Opportunities.BioMed research international · 2026Review
- PIEZO2 in tumors: from mechanobiological switches to activity-targeted therapies.Journal of experimental & clinical cancer research : CR · 2025Review
- The Emerging Role of CKAP4 in GI Cancer: From Molecular Pathways to Clinical Applications.Current oncology (Toronto, Ont.) · 2025Review
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- Cytoskeleton-associated protein 4: a double-edged sword in cell growth and aging.Biogerontology · 2025Review
- Mechanisms and Therapeutic Strategies for Minority Cell-Induced Paclitaxel Resistance and Tumor Progression Mediated by Mechanical Forces.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Crosstalk Between Phase-Separated Membraneless Condensates and Membrane-Bound Organelles in Cellular Function and Disease.Advances in experimental medicine and biology · 2025Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Solid stress, originating from rigid and elastic components of extracellular matrix and cells, is a typical physical hallmark of tumors. Mounting evidence indicates that elevated solid stress drives metastasis and affects prognosis. However, the molecular mechanism of how cancer cells sense solid stress, thereby exacerbating malignancy, remains elusive. In this study, our clinical data suggest that elevated stress in metastatic solid tumors is highly associated with the expression of cytoskeleton-associated protein 4 (CKAP4). Intriguingly, CKAP4, as a sensitive intracellular mechanosensor, responds specifically to solid stress in a subset of studied tumor micro-environmental elements through liquid-liquid phase separation. These micron-scaled CKAP4 puncta adhere tightly onto microtubules and dramatically reorchestrate their curvature and branching to enhance cell spreading, which, as a result, boosts cancer cell motility and facilitates distant metastasis in vivo. Mechanistically, the intrinsically disordered region 1 (IDR1) of CKAP4 binds to microtubules, while IDR2 governs phase separation due to the Ca
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Registered trials
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