Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Язык: Английский

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New opportunities and old challenges in the clinical translation of nanotheranostics

Nature Reviews Materials, Год журнала: 2023, Номер 8(12), С. 783 - 798

Опубликована: Июль 26, 2023

Язык: Английский

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Beyond matrix stiffness: targeting force-induced cancer drug resistance

Trends in cancer, Год журнала: 2023, Номер 9(11), С. 937 - 954

Опубликована: Авг. 8, 2023

During tumor progression, mechanical abnormalities in the microenvironment (TME) trigger signaling pathways cells that activate cellular programs, resulting growth and drug resistance. In this review, we describe mechanisms of action for anti-cancer therapies mechanotransduction programs regulate processes, including cell proliferation, apoptosis, survival phenotype switching. We discuss how therapeutic response is impacted by three main TME abnormalities: high extracellular matrix (ECM) composition stiffness; interstitial fluid pressure (IFP); elevated forces. also review drugs normalize these or block mechanosensors pathways. Finally, current challenges perspectives development new strategies targeting mechanically induced resistance clinic.

Язык: Английский

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Cell response to mechanical microenvironment cues via Rho signaling: From mechanobiology to mechanomedicine

Acta Biomaterialia, Год журнала: 2023, Номер 159, С. 1 - 20

Опубликована: Янв. 28, 2023

Язык: Английский

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Metformin-based nanomedicines for reprogramming tumor immune microenvironment

Theranostics, Год журнала: 2024, Номер 15(3), С. 993 - 1016

Опубликована: Дек. 2, 2024

Immunotherapy has transformed current cancer management, and it achieved significant progress over last decades. However, an immunosuppressive tumor microenvironment (TME) diminishes the effectiveness of immunotherapy by suppressing activity immune cells facilitating immune-evasion. Adenosine monophosphate-activated protein kinase (AMPK), a key modulator cellular energy metabolism homeostasis, gained growing attention in anti-tumor immunity. Metformin is usually considered as cornerstone diabetes its role activating AMPK pathway also been extensively explored therapy although findings on remain inconsistent. nanomedicine formulation found to hold potential reprogramming TME through immunometabolic modulation both cells. This review elaborates foundation via metformin-based nanomedicines, offering valuable insights for next generation therapy.

Язык: Английский

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PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes

Nature Biomedical Engineering, Год журнала: 2024, Номер 8(9), С. 1162 - 1176

Опубликована: Март 21, 2024

Язык: Английский

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Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 23, 2025

The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising diverse array of cellular non-cellular components that precisely orchestrate pivotal behaviors, including invasion, metastasis, drug resistance. While unraveling the interplay between behaviors represents tremendous challenge, recent research illuminates crucial biological phenomenon known mechanotransduction. Within microenvironment, mechanical cues like tensile stress, shear stiffness play role by activating mechanosensitive effectors such PIEZO proteins, integrins, Yes-associated protein. This activation initiates cascades intrinsic signaling pathways, effectively linking physical properties tissues to their physiological pathophysiological processes morphogenesis, regeneration, immunity. mechanistic insight offers novel perspective on how within impact behaviors. intricacies are yet be fully elucidated, it exhibits distinct attributes from non-malignant tissues, elevated solid stresses, interstitial hypertension, augmented matrix stiffness, enhanced viscoelasticity. These traits exert notable influences progression treatment responses, enriching our comprehension multifaceted nature microenvironment. Through this innovative review, we aim provide new lens decipher contexts, broadening knowledge these factors promote or inhibit thus offering valuable insights identify potential targets for anti-tumor strategies.

Язык: Английский

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Sonodynamic-immunomodulatory nanostimulators activate pyroptosis and remodel tumor microenvironment for enhanced tumor immunotherapy

Theranostics, Год журнала: 2023, Номер 13(5), С. 1571 - 1583

Опубликована: Янв. 1, 2023

Rationale: Spatiotemporal control of pyroptosis has a profound impact on cancer immunotherapy.Owing to the precise spatiotemporal and reduction in side effects ultrasound (US), sonodynamic therapy (SDT) is expected be promising mean activate pyroptosis.Furthermore, pyroptosis-initiated immune response can amplified by enhanced lymphocyte infiltration occurring due extracellular matrix (ECM) depletion.Therefore, it highly desirable develop sonodynamic-immunomodulatory strategy amplify pyroptosis-mediated tumor immunotherapy remodeling microenvironment, thereby enhancing immunotherapy.Methods: We reported potent based sonosensitizer, which composed LY364947-loaded porous coordination network (PCN-224) camouflaged with red blood cell (RBC) membrane evaluated activation, collagen depletion, immunocyte infiltration, adaptive during vitro vivo.Results: The sonosensitizer generated reactive oxygen species (ROS) under US irradiation initiated caspase-3 apoptotic signaling pathway, regarded as key upstream activator gasdermin E (GSDME)-mediated pyroptosis.During subsequent anti-tumor mediated pyroptosis, LY364947 loosened ECM structure via resulting T-lymphocyte nearly complete eradication tumors mouse model formation immunological memory. Conclusion:Our findings indicate that pyroptotic exhibits robust efficacy well provides novel insights into role immunology.

Язык: Английский

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Zinc‐Organometallic Framework Vaccine Controlled‐Release Zn²⁺ Regulates Tumor Extracellular Matrix Degradation Potentiate Efficacy of Immunotherapy

Advanced Science, Год журнала: 2023, Номер 10(27)

Опубликована: Июль 13, 2023

Abstract Tumor extracellular matrix (ECM) not only forms a physical barrier for T cells infiltration, but also regulates multiple immunosuppressive pathways, which is an important reason immunotherapy failure. The cyclic guanosine monophosphate‐adenosine monophosphate synthase‐stimulator of interferon genes (cGAS‐STING) pathway plays key role in activating CD8 + cells, maintaining stemness and enhancing the antitumor effect. Herein, zinc‐organometallic framework vaccine (ZPM@OVA‐CpG) prepared by self‐assembly, achieves site‐directed release Zn 2+ dendritic cell (DC) lysosomes tumor microenvironment under acidic conditions, reported. actively targets DC, significantly enhances cGAS‐STING signal, promotes DC maturation antigen cross‐presentation, induces strong activation cells. Meanwhile, reaches site, releasing , up‐regulates activity metalloproteinase‐2, degrades various collagen components ECM, effectively alleviates immune suppression, infiltration killing ZPM@OVA‐CpG solves problem low delivery efficiency weak ability, degradation ECM via first time, providing promising therapeutic platform development efficient novel vaccines.

Язык: Английский

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Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease

Biomolecules, Год журнала: 2024, Номер 14(9), С. 1186 - 1186

Опубликована: Сен. 20, 2024

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are essential components of the extracellular matrix (ECM) with pivotal roles in cellular mechanosensing pathways. GAGs, such as heparan sulfate (HS) chondroitin (CS), interact various cell surface receptors, including integrins receptor tyrosine kinases, to modulate responses mechanical stimuli. PGs, comprising a core protein covalently attached GAG chains, serve dynamic regulators tissue mechanics behavior, thereby playing crucial role maintaining homeostasis. Dysregulation GAG/PG-mediated pathways is implicated numerous pathological conditions, cancer inflammation. Understanding intricate mechanisms by which GAGs PGs forces holds promise for developing novel therapeutic strategies targeting mechanotransduction disease. This comprehensive overview underscores importance key mediators homeostasis their potential targets mitigating mechano-driven pathologies, focusing on

Язык: Английский

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