ArticleCell death & disease2019
Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
- Nanomedicine beyond carriers - devices, cells & living therapeutics.Biomedical microdevices · 2026Review
- Cyclic mechanical stretch suppresses intrinsic apoptosis in high metastatic melanoma.Materials today. Bio · 2026Article
- Piezo1 in the central nervous system: decoding the mechanical signature of neuroinflammation.Journal of neuroinflammation · 2026Review
- Piezo1-ATF3-PPP1r15a Axis Transduces Mechanical Stress into Apoptosis in Glioma Under Low-Intensity Focused Ultrasound.Cancers · 2026Article
- Fluoxetine Acts as a Calcium-Dependent Sensitizer of TRAIL-Induced Apoptosis in Glioblastoma Multiforme.ACS omega · 2026Article
- Fluid shear stress activates a targetable mechano-metastatic cascade to promote medulloblastoma metastasis.Nature biomedical engineering · 2026Article
- Article
- The Dual Role of Piezo1 in Cancer: Mechanotransduction, Microenvironment Remodelling, and Therapeutic Opportunities.Drug design, development and therapy · 2026Review
- Piezo1 Upregulation in Monocyte-Derived Macrophages Impairs Post-Myocardial Infarction Cardiac Repair via Defective Efferocytosis and Enhanced Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The electrical tumor microenvironment: abnormalities and opportunities.Frontiers in oncology · 2026Review
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- Piezo1 promotes EMT and tumor progression in HNSCC through a YAP1-Associated Galectin-1 axis.Frontiers in cell and developmental biology · 2026Article
- Capillary constrictions prime cancer cell tumorigenicity through PIEZO1.Nature communications · 2025Article
- Article
- Opposing Calcium-Dependent Effects of GsMTx4 in Acute Lymphoblastic Leukemia: In Vitro Proliferation vs. In Vivo Survival Advantage.International journal of molecular sciences · 2025Article
- Mechanical Loading of Osteocytes via Oscillatory Fluid Flow Regulates Early-Stage PC-3 Prostate Cancer Metastasis to Bone.Advanced biology · 2025Article
- Applying Ultrasound to Mechanically and Noninvasively Sensitize Prostate Tumors to TRAIL-Mediated Apoptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Meeting Review: "National Cancer Institute Conference on Cancer Bioelectricity" September 12, 2024.Bioelectricity · 2025Review
- Piezo1-related physiological and pathological processes in glioblastoma.Frontiers in cell and developmental biology · 2025Review
- The dual role of Piezo1 in tumor cells and immune cells: a new target for cancer therapy.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
TRAIL specifically induces apoptosis in cancer cells without affecting healthy cells. However, TRAIL's cancer cytotoxicity was insufficient in clinical trials. Circulatory-shear stress is known to sensitize cancer cells to TRAIL. In this study, we examine the mechanism of this TRAIL sensitization with the goal of translating it to static conditions. GsMTx-4, a Piezo1 inhibitor, was found to reduce shear stress-related TRAIL sensitization, implicating Piezo1 activation as a potential TRAIL-sensitizer. The Piezo1 agonist Yoda1 recreated shear stress-induced TRAIL sensitization under static conditions. A significant increase in apoptosis occurred when PC3, COLO 205, or MDA-MB-231 cells were treated with Yoda1 and TRAIL in combination, but not in Bax-deficient DU145 cells. Calpastatin inhibited apoptosis in Yoda1-TRAIL treated cells, indicating that calpain activation is necessary for apoptosis by Yoda1 and TRAIL. Yoda1 and TRAIL treated PC3 cells showed increased mitochondrial outer membrane permeability (MOMP), mitochondrial depolarization, and activated Bax. This implies that Piezo1 activation sensitizes cancer cells to TRAIL through a calcium influx that activates calpains. The Calpains then induce MOMP by enhancing Bax activation. From these experiments a computational model was developed to simulate apoptosis for cells treated with TRAIL and increased calcium. The computational model elucidated the proapoptotic or antiapoptotic roles of Bax, Bcl-2, XIAP, and other proteins important in the mitochondrial-apoptotic signaling pathway.
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