The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2135 - 2135

Published: Feb. 10, 2024

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research suggests that they may regulated by both shared pathways. Specifically, recent studies indicated CIP CIL utilize mechanotransduction pathways, process involves cells sensing responding to mechanical forces. This review article describes role in CI, shedding light on how forces regulate CIP. Emphasis is placed filamin A (FLNA)-mediated mechanotransduction, elucidating FLNA senses translates them biochemical signals cell proliferation. In addition FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable directly indirectly binding specific DNA sequences distant genes gene expression, emerge sensitive players signaling pathways CI. presents methods identifying these TAF profiling associated changes chromatin structure, offering valuable insights other biological functions mediated mechanotransduction. Finally, it addresses unanswered questions fields delineates their possible future directions.

Language: Английский

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The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Language: Английский

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Biomechanical forces and force-triggered drug delivery in tumor neovascularization

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116117 - 116117

Published: Jan. 3, 2024

Tumor angiogenesis is one of the typical hallmarks tumor occurrence and development, neovascularization also exhibits distinct characteristics from normal blood vessels. As number cells matrix inside increases, biomechanical force enhanced, specifically manifested as solid stress, fluid stiffness, topology. This mechanical microenvironment provides shelter for tumors intensifies angiogenesis, providing oxygen nutritional support progression. During emerges, which in turn feeds back to regulate progression, including biochemical signals can angiogenesis. Blood vessels possess inherent sensitivity stimuli, but compared extensive research on signal regulation, study regulation by remains relatively scarce. Biomechanical forces affect phenotypic signaling pathways vessels, directly regulating Meanwhile, they indirectly causing an imbalance affecting stromal cell function. Understanding regulatory mechanism beneficial better identifying even taming involved new therapeutic targets vascular normalization. Therefore, we summarized composition their direct or indirect neovascularization. In addition, this review discussed use combination with anti-angiogenic therapies treatment tumors, triggered delivery systems.

Language: Английский

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High-viscosity driven modulation of biomechanical properties of human mesenchymal stem cells promotes osteogenic lineage

Materials Today Bio, Journal Year: 2024, Volume and Issue: 26, P. 101058 - 101058

Published: April 17, 2024

Biomechanical cues could effectively govern cell gene expression to direct the differentiation of specific stem lineage. Recently, medium viscosity has emerged as a significant mechanical stimulator that regulates cellular properties and various physiological functions. However, whether can regulate human mesenchymal cells (hMSCs) trigger osteogenic remains uncertain. The mechanism by which sense respond changes in viscosity, promote lineage, elusive. In this study, we demonstrated hMSCs, cultured high-viscosity medium, exhibited larger spreading area higher intracellular tension, correlated with elevated formation actin stress fibers focal adhesion maturation. Furthermore, these observed hMSCs were associated activation TRPV4 (transient receptor potential vanilloid sub-type 4) channels on membrane. This feedback loop among activation, tension results calcium influx, subsequently promotes nuclear localization NFATc1 (nuclear factor activated T 1). Concomitantly, induced deformation promoted YAP (YES-associated protein). concurrent significantly enhanced alkaline phosphatase (ALP) for pre-osteogenic activity. Taken together, findings provide more comprehensive view how viscosity-induced alterations biomechanical MSCs impact osteogenesis-related genes, ultimately

Language: Английский

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Force-sensing protein expression in response to cardiovascular mechanotransduction

EBioMedicine, Journal Year: 2024, Volume and Issue: 110, P. 105412 - 105412

Published: Oct. 31, 2024

Language: Английский

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Integrating single‐cell and spatial analysis reveals MUC1‐mediated cellular crosstalk in mucinous colorectal adenocarcinoma

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(5)

Published: May 1, 2024

Abstract Background Mucinous colorectal adenocarcinoma (MCA) is a distinct subtype of cancer (CRC) with the most aggressive pattern, but effective treatment MCA remains challenge due to its vague pathological characteristics. An in‐depth understanding transcriptional dynamics at cellular level critical for developing specialised strategies. Methods We integrated single‐cell RNA sequencing and spatial transcriptomics data systematically profile tumor microenvironment (TME), particularly interactome stromal immune cells. In addition, three‐dimensional bioprinting technique, canonical ex vivo co‐culture system, immunofluorescence staining were further applied validate communication networks within TME. Results This study identified crucial intercellular interactions that engaged in pathogenesis. found increased infiltration FGF7 + / THBS1 myofibroblasts tissues decreased expression genes associated leukocyte‐mediated immunity T cell activation, suggesting role these cells regulating immunosuppressive MS4A4A macrophages exhibit M2‐phenotype enriched tumoral niche high was poor prognosis cohort data. The ligand‐receptor‐based analysis revealed tight interaction MUC1 malignant ZEB1 endothelial cells, providing mechanistic information angiogenesis molecular targets subsequent translational applications. Conclusions Our provides novel insights into communications among tumour are significantly TME during progression, presenting potential prognostic biomarkers therapeutic strategies MCA. Key points Tumour profiling developed. interplay promote development. M2 phenotype endotheliocytes engage EndMT process

Language: Английский

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Substrate viscoelasticity affects human macrophage morphology and phagocytosis

Soft Matter, Journal Year: 2023, Volume and Issue: 19(13), P. 2438 - 2445

Published: Jan. 1, 2023

Using viscoelastically-tunable polyacrylamide hydrogels, we show that macrophage morphology and phagocytosis depend on substrate loss modulus, indicating viscoelasticity may be an important design parameter in immunomodulatory biomaterials.

Language: Английский

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Biomaterials regulates BMSCs differentiation via mechanical microenvironment

Biomaterials Advances, Journal Year: 2023, Volume and Issue: 157, P. 213738 - 213738

Published: Dec. 22, 2023

Language: Английский

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Local Concentrations of TGF-β1 and IGF-1 Appear Determinant in Regulating Bone Regeneration in Human Postextraction Tooth Sockets

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8239 - 8239

Published: May 4, 2023

Healing after tooth extraction involves a series of reparative processes affecting both alveolar bone and soft tissues. The aim the present study was to investigate whether activation molecular signals during healing process confers regenerative advantage socket tissue (ESsT) at 8 weeks healing. Compared subepithelial connective graft (CTG), qRT-PCR analyses revealed dramatic enrichment ESsT in osteogenic differentiation markers. However, CTG shared characteristics nonspecialized by expressing comparable levels genes encoding abundant extracellular matrix (ECM) proteins. Genes transforming growth factor-β1 (TGF-β1) its receptors were strongly enriched CTG, whereas transcript for insulin-like factor-1 (IGF-1) showed significantly high expression Mechanical stimulation, means cyclic strain or stiffness applied primary cells (ESsT-C) fibroblasts (CTG-F) extracted from samples, that stress-induced TGF-β1 not exceeding 2.3 ng/mL, as measured ELISA, combination with IGF-1 up 2.5 ng/mL able induce potential ESsT-Cs. stiff matrices (50 kPa), upregulating 6.6 caused downregulation gene In CTG-Fs, endogenous ≥ 4.6 likely responsible complete lack osteogenesis. Treatment ESsT-Cs proved that, specific concentrations, two factors exhibited either an inductive-synergistic suppressive activity, thus determining mineralization Taken together, our data warrant clinical exploration augmentative procedures dental implant placement surgeries.

Language: Английский

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High Stretch Associated with Mechanical Ventilation Promotes Piezo1-Mediated Migration of Airway Smooth Muscle Cells

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1748 - 1748

Published: Feb. 1, 2024

Ventilator-induced lung injury (VILI) during mechanical ventilation (MV) has been attributed to airway remodeling involving increased smooth muscle cells (ASMCs), but the underlying mechanism is not fully understood. Thus, we aimed investigate whether MV-associated high stretch (>10% strain) could modulate mechanosensitive Piezo1 expression and thereby alter cell migration of ASMCs as a potential pathway in VILI. C57BL/6 mice were subjected MV at tidal volume (VT, 18 mL/kg, 3 h) (13% strain, 0.5 Hz, 72 h), respectively. Subsequently, or evaluated for integrin mRNA by immunohistochemical staining quantitative PCR (qPCR), adhesion transwell assays. Cells either treated with siRNA, Piezo1-eGFP, knockin, Y27632, blebbistatin regulate inhibit Rho-associated kinase (ROCK) signaling prior assessment. We found that situ tissue, αVβ1 isolated from all reduced primary (pASMCs) was greatly enhanced. Similarly, line mouse (mASMCs) cultured vitro showed Interestingly, such effects on be induced abolished/reversed down/up-regulation inhibition ROCK signaling. High associated appears modulator can, thus, promote therapeutic MV. This may novel detrimental MV, and, therefore, intervention target treat

Language: Английский

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