ArticleScience advances2025
Local soft niches in mechanically heterogeneous primary tumors promote brain metastasis via mechanotransduction-mediated HDAC3 activity.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Mechanical memory as a metastatic compass: a comparative framework for understanding organotropism through biophysical priming.Cancer metastasis reviews · 2026Review
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Elucidation of ACAT1's role in hepatic ischemia-reperfusion injury: TFEB-mediated mitophagy and ferroptosis modulation as therapeutic targets.Journal of pharmaceutical analysis · 2026Article
- Mechanoadaptation via Myosin Cytoplasmic Redistribution Protects Circulating Tumor Cells From Shear-induced Death During Hematogenous Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nuclear Mechanotransduction Across the Metastatic Cascade: Decoding Spatiotemporal Heterogeneity in Cancer Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Piezo channels in tumors.Journal of cancer research and clinical oncology · 2026Review
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- Sulforaphane as a Multi-Scale Mechano-Modulator in Cancer: An Integrative Perspective.Biology · 2026Article
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- Polycystin-1 Orchestrates Tumor Context-Dependent Mechanotransduction Programs Driving Epithelial-to-Mesenchymal Transition and Invasion in Solid Cancers.International journal of biological sciences · 2026Article
- Multi-omics investigation reveals molecular determinants of cancer cell evolution on soft extracellular matrix.bioRxiv : the preprint server for biology · 2025Article
- 3D printing-biomimetic local stiff niche enhances glycolysis to boost PDAC cell stem-like phenotype via N6-methyladenosine-suppressed YAP1 mRNA decay.Materials today. Bio · 2025Article
- Intercellular contractile force attenuates chemosensitivity through Notch-MVP-mediated nuclear drug export.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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Abstract
Tumor cells with organ-specific metastasis traits arise in primary lesions with substantial variations of local niche mechanics owing to intratumoral heterogeneity. However, the roles of mechanically heterogeneous primary tumor microenvironment in metastatic organotropism remain an enigma. This study reports that persistent priming in soft but not stiff niches that mimic primary tumor mechanical heterogeneity induces transcriptional reprogramming reminiscent of neuron and promotes the acquisition of brain metastatic potential. Soft-primed cells generate brain metastases in vivo through enhanced transendothelial migration across blood-brain barrier and brain colonization, which is further supported by the findings that tumor cells residing in local soft niches of primary xenografts exhibit brain metastatic tropism. Mechanistically, soft niches suppress cytoskeleton-nucleus-mediated mechanotransduction, which promotes histone deacetylase 3 activity. Inhibiting histone deacetylase 3 abolishes niche softness-induced brain metastatic ability. Collectively, this study uncovers a previously unappreciated role of local niche softness within primary tumors in brain metastasis, highlighting the significance of primary tumor mechanical heterogeneity in metastatic organotropism.
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