Tight Junction Structure and Function Revisited

Trends in Cell Biology, Год журнала: 2020, Номер 30(10), С. 805 - 817

Опубликована: Сен. 2, 2020

Язык: Английский

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Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Март 11, 2023

The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation distant metastasis. Anticancer treatments including adjuvant therapies targeted are effective in eliminating cancer cells but limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role development through changes macromolecule components, degradation enzymes stiffness. These variations under control cellular components tissue via aberrant activation signaling pathways, interaction ECM to multiple surface receptors, mechanical impact. Additionally, shaped regulates immune which results suppressive microenvironment hinders efficacy immunotherapies. Thus, acts as barrier protect from supports progression. Nevertheless, profound regulatory network remodeling hampers design individualized antitumor treatment. Here, we elaborate on composition ECM, discuss specific mechanisms remodeling. Precisely, highlight impact development, proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, escape. Finally, emphasize "normalization" potential strategy for anti-malignant

Язык: Английский

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Liposomes Under Shear: Structure, Dynamics, and Drug Delivery Applications

Advanced NanoBiomed Research, Год журнала: 2023, Номер 3(4)

Опубликована: Фев. 5, 2023

The targeted delivery to specific locations while not causing damage healthy tissues efficiently remains a challenge in drug systems. Through addressing this issue, stimuli‐responsive materials have been under investigation. As one of the fundamental forces associated with blood flow, shear stress is taken as an advantage design shear‐sensitive carriers. Although flow modeled laminar normal conditions, case constrictions caused by endothelial stress, cardiovascular diseases, or angiogenesis due tumor formation, local can dramatically increase. To date, investigated two main categories: shear‐disaggregated and shear‐deformed nanoparticles based on their structural mechanism after exposure high‐shear stress. Among them, liposomes are promising soft deformable structure, high biocompatibility, controlled‐release properties, sensitivity Herein, review, effects terms changes, regimes, rheological applications discussed. It believed that work provides basis for designing more effective systems considering complexity human body.

Язык: Английский

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Cell Adhesion at the Tight Junctions: New Aspects and New Functions

Cells, Год журнала: 2023, Номер 12(23), С. 2701 - 2701

Опубликована: Ноя. 24, 2023

Tight junctions (TJ) are cell–cell adhesive structures that define the permeability of barrier-forming epithelia and endothelia. In contrast to this seemingly static function, TJs display a surprisingly high molecular complexity unexpected dynamic regulation, which allows maintain barrier in presence physiological forces response perturbations. Cell–cell adhesion receptors play key roles during regulation TJs. They connect individual cells within cellular sheets link sites contacts underlying actin cytoskeleton. Recent findings support transmitting mechanical promoting phase separation. review, we discuss newly discovered functions cell localized at their role function.

Язык: Английский

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Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex

The Journal of Cell Biology, Год журнала: 2024, Номер 223(5)

Опубликована: Март 22, 2024

Epithelia must be able to resist mechanical force preserve tissue integrity. While intercellular junctions are known important for the resistance of epithelia, roles tight (TJs) remain established. We previously demonstrated that epithelial cells devoid TJ membrane proteins claudins and JAM-A completely lack TJs exhibit focal breakages their apical junctions. Here, we demonstrate fracture when claudin/JAM-A–deficient undergo spontaneous cell stretching. The junction was accompanied by actin disorganization, polymerization required integrity in cells. Further deletion CAR resulted disruption ZO-1 molecule ordering at junctions, severe defects These results regulate junctional complex

Язык: Английский

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Circular RNA hsa_circ_0004277 Stimulates Malignant Phenotype of Hepatocellular Carcinoma and Epithelial-Mesenchymal Transition of Peripheral Cells

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 8

Опубликована: Янв. 12, 2021

Accumulating evidence shows that exosomal circRNAs reflect the physiological status of donor cells, and various cell reactions are induced after captured by recipient cells. In this study, qRT-PCR was performed to detect circ-0004277 expression in hepatocellular carcinoma (HCC) lines, tissues, plasma exosomes. The effects on proliferation migration HCC cells were assessed counting, 5-ethynyl-2′-deoxyuridine assays, Transwell tumor formation nude mice. We found significantly upregulated exosomes compared normal controls. Overexpression enhanced proliferation, migration, epithelial-mesenchymal transition (EMT) vivo vitro . Furthermore, from surrounding stimulated EMT progression. ZO-1, a tight junction adapter protein, downregulated tissues. conclusion, our findings suggest promotes malignant phenotype via inhibition ZO-1 promotion addition, stimulates peripheral through cellular communication further promote invasion into

Язык: Английский

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The Epithelial Cell Leak Pathway

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(14), С. 7677 - 7677

Опубликована: Июль 18, 2021

The epithelial cell tight junction structure is the site of transepithelial movement solutes and water between cells (paracellular permeability). Paracellular permeability can be divided into two distinct pathways, Pore Pathway mediating small ions Leak large solutes. Claudin proteins form basic paracellular barrier mediate via Pathway. remains less understood. Several have been implicated in Pathway, including occludin, ZO proteins, tricellulin, actin filaments, but comprising remain unresolved. Many aspects such as its molecular mechanism, properties, regulation, controversial. In this review, we provide a historical background to evolution concept from initial examinations permeability. We then discuss current information about properties present theories for Finally, some recent research suggesting possible basis

Язык: Английский

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ZO-1 Guides Tight Junction Assembly and Epithelial Morphogenesis via Cytoskeletal Tension-Dependent and -Independent Functions

Cells, Год журнала: 2022, Номер 11(23), С. 3775 - 3775

Опубликована: Ноя. 25, 2022

Formation and maintenance of tissue barriers require the coordination cell mechanics cell-cell junction assembly. Here, we combined methods to modulate ECM stiffness measure mechanical forces on adhesion complexes investigate how tight junctions regulate epithelial morphogenesis. We found that depletion adaptor ZO-1 disrupted assembly morphogenesis in an stiffness-dependent manner led a stiffness-dependant reorganisation active myosin. Both formation were rescued by inhibition actomyosin contractility. also impacted tension at cell-matrix E-cadherin-based adhesions. The effect E-cadherin depended correlated with effects actin cytoskeleton organisation. However, knockout revealed tension-independent functions ZO-1. ZO-1-deficient cells could assemble functional low tension, but their remained corrupted strongly reduced discontinuous recruitment junctional components. Our results thus reveal reciprocal regulation between controls morphogenesis, that, second, step, is required morphologically structurally fully assembled functionally normal junctions.

Язык: Английский

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Force-dependent remodeling of cytoplasmic ZO-1 condensates contributes to cell-cell adhesion through enhancing tight junctions

iScience, Год журнала: 2022, Номер 25(2), С. 103846 - 103846

Опубликована: Фев. 1, 2022

The physiological importance of biomolecular condensates is widely recognized, but how it controlled in time and space during development largely unknown. Here, we show that a tight junction protein ZO-1 forms cytoplasmic the trophectoderm (TE) mouse embryo before E4.0. These disappear via dissolution, accumulates at cell as blastocyst cavity grows internal pressure on TE cells increases. In contrast, this dissolution was less evident attached to inner mass because they receive weaker tensile forces. Furthermore, analyses using MDCK demonstrated are generated maintained by liquid-liquid phase separation. Our study also highlights dynamics these depends physical environment an interaction between F-actin. We propose force-dependent regulation condensation contributes establishment robust cell-cell adhesion early development.

Язык: Английский

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Nuclear lamina strain states revealed by intermolecular force biosensor

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 30, 2023

Abstract Nuclear lamins have been considered an important structural element of the nucleus. The nuclear lamina is thought both to shield DNA from excessive mechanical forces and transmit onto DNA. However, date there not yet a technical approach directly measure on at protein level. To overcome this limitation, we developed nanobody-based intermolecular tension FRET biosensor capable measuring strain lamin filaments. Using sensor, were able show that subjected significant force. These are dependent volume, actomyosin contractility, functional LINC complex, chromatin condensation state, cell cycle, EMT. Interestingly, large also present nucleoplasmic lamins, indicating these may role in Overall, demonstrate allows construction biosensors for complex structures mechanobiology studies.

Язык: Английский

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