Tissue Mechanics and Hedgehog Signaling Crosstalk as a Key Epithelial–Stromal Interplay in Cancer Development

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 8, 2024

Abstract Epithelial‐stromal interplay through chemomechanical cues from cells and matrix propels cancer progression. Elevated tissue stiffness in potentially malignant tissues suggests a link between enhanced tumor growth. In this study, employing chronic oral/esophageal injury models, it is demonstrated that epithelial–stromal Hedgehog (Hh) signaling key compounding development. Epithelial actively interact with fibroblasts, exchanging mechanoresponsive signals during the precancerous stage. Specifically, epithelial release Sonic Hh, activating fibroblasts to produce proteins remodeling enzymes, resulting stiffening. Subsequently, basal adjacent stiffened become proliferative undergo epithelial‐to‐mesenchymal transition, acquiring migratory invasive properties, thereby promoting Notably, transcriptomic programs of oncogenic GLI2, mechano‐activated by actin cytoskeletal tension, govern process, elucidating crucial role non‐canonical GLI2 activation orchestrating proliferation mesenchymal transition cells. Furthermore, pharmacological intervention targeting stiffening proves highly effective slowing These findings underscore impact epithelial‐stromal chemo‐mechanical (Hh‐stiffness) development, suggest holds promise as strategy disrupt feedback, enabling treatment.

Language: Английский

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Extracellular matrix-dependent regulation of Septin 7 in focal adhesions promotes mechanosensing and functional response in fibroblasts

iScience, Journal Year: 2024, Volume and Issue: 27(12), P. 111355 - 111355

Published: Nov. 9, 2024

Fibroblasts are adherent cells that maintain tissue homeostasis by sensing and responding to the extracellular matrix (ECM). Focal adhesions (FAs) link these ECM changes actomyosin dynamics through in its composition, influencing cellular response. Septin-7 (Sept-7) has previously been found FA proteomics studies shown influence sensing. Using total internal reflection microscopy, we ECM-mediated integrin activation regulates spatially distinct Sept-7 structures FAs. In perinuclear regions, binding stabilized bundles at back of FAs, while core peripheral FAs high promoted elongation structures. Ventral were crucial for sensing, impacting region-specific elongation, stabilization, contributing fibroblast mechanosensitivity. Taken together, our results suggest integrin-dependent regulation ventral plays a pivotal role mechanotransduction recruitment assembly into subpopulations.

Language: Английский

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Synthesis and Comprehensive Characterization of PVA/Chitosan/Cu Nanowires Wound Dressing Hydrogel for Effective In Vitro Wound Healing

Journal of Industrial and Engineering Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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A biomechanical model for cell sensing and migration

Computer Methods in Biomechanics & Biomedical Engineering, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19

Published: Nov. 13, 2024

We developed an original computational model for cell deformation and migration capable of accounting the sensitivity to environment its appropriate adaptation. This is ultimately intended be used address tissue morphogenesis. Hence it has been designed comply with four requirements: (1) should able probe sense respond accordingly; (2) easy parametrize adapt different types; (3) extend 3D cases; (4) simulations fast enough integrate many interacting cells. The carried out focused on two aspects: first, general behaviour a homogeneous substrate, as observed experimentally, validation. enabled us decipher mechanisms by which can migrate, highlighting respective influences adhesions lifetimes their traction; second, predicts anisotropic patterned in agreement recently published experiments. results show that mechanosensors simulated make possible reproduce such experiments terms bias generated substrate anisotropy. Here again, provides biomechanical explanation this phenomenon, depending cell-matrix interactions adhesion maturation rate.

Language: Английский

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Dysregulation of septin cytoskeletal organization in the trabecular meshwork contributes to ocular hypertension

JCI Insight, Journal Year: 2024, Volume and Issue: 9(23)

Published: Dec. 5, 2024

Ocular hypertension, believed to result partly from increased contractile activity, cell adhesive interactions, and stiffness within the trabecular meshwork (TM), is a major risk factor for glaucoma, leading cause of blindness. However, identity molecular mechanisms governing organization actomyosin interactions in TM remains limited. Based on our previous findings, which proteomics analyses revealed elevated levels septins, including septin-9 human cells treated with ocular hypertensive agent dexamethasone, here, we evaluated effects overexpression, deficiency, pharmacological targeting cells. These studies demonstrated profound impact organization, adhesion, contraction, phagocytosis. Overexpression raised intraocular pressure (IOP) mice, while inhibition permeability. In addition, replicated significant association between common variant (rs9038) SEPT9 IOP Genetic Epidemiology Research Adult Healthy Aging (GERA) cohort. Collectively, these data reveal link dysregulated septin cytoskeletal IOP, likely due enhanced fibrotic activity. This suggests that cytoskeleton could offer novel approach lowering patients glaucoma.

Language: Английский

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