ArticleScience advances2026
Compressive stress-driven Piezo1 activation and Rho-ROCK mechanotransduction promote tumor progression via epigenetic mechanical memory.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Mechanical regulation of cell memory.Nature structural & molecular biology · 2026Review
- Dynamic control of cell state transitions during tissue morphogenesis.The EMBO journal · 2026Review
- Nanomedicine targeting ECM stiffness: restoring mechanical homeostasis for cancer immunotherapy.Materials today. Bio · 2026Review
- Mechanical forces of beating heart suppress cancer growth.Mechanobiology in medicine · 2026Article
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- Neural regulation of immune evasion in breast cancer: a multiscale neuro-immune framework.Frontiers in immunology · 2026Review
- The Dual Role of Piezo1 in Cancer: Mechanotransduction, Microenvironment Remodelling, and Therapeutic Opportunities.Drug design, development and therapy · 2026Review
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Authors and funding
9 authors.
Funding
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Abstract
Rapidly growing tumors experience high tissue-level forces, particularly when growing within a restricted space. These require counteracting by intracellular forces to prevent tissue damage. Here, we reveal the ion channel Piezo1 as a mechanosensor of compressive force, activating Rho-Rho kinase (ROCK) mechanotransduction to generate intracellular forces and enhancing malignant characteristics of tumors. Compressive stress promoted cancer growth in vivo in a Rho-ROCK-dependent manner. Silencing Piezo1 abolished compression-induced Rho-ROCK activation and tumor progression in this model. Accordingly, elevated PIEZO1 is associated with 35% poorer survival of patients with breast cancer. We show that acute compressive forces engender epigenetic mechanical memory via Piezo1-activated Rho-ROCK signaling, promoting tumor growth in vivo. Compressive stress promoted ROCK-dependent histone modifications associated with open chromatin, including acetylation of key histone 3-lysine residues, regulating the expression of cancer-related genes across cell, explant, and in vivo tumor models. Our observations suggest that the PIEZO1-RHO-ROCK axis links tissue-level forces to persistent tumor-promoting epigenetic changes and merits evaluation as a mechanotherapy target in cancer.
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