c-Src induced vascular malformations require localised matrix degradation at focal adhesions DOI Creative Commons
Patricia Essebier, Lilian Schimmel,

Teodor E. Yordanov

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 15, 2023

Abstract Endothelial cells lining the blood vessel wall communicate intricately with surrounding extracellular matrix, translating mechanical cues into biochemical signals. Moreover, vessels require capability to enzymatically degrade matrix them, facilitate vascular expansion. c-Src plays a key role in growth, its loss endothelium reducing sprouting and focal adhesion signalling. Here, we show that constitutive activation of endothelial results rapid expansion, operating independently growth factor stimulation or fluid shear stress forces. This is driven by an increase signalling size, enhancement localised secretion metalloproteinases responsible for remodelling. Inhibition metalloproteinase activity robust rescue expansion elicited heightened activity. supports premise moderating adhesion-related events degradation can counteract abnormal implications pathologies unusual morphologies.

Language: Английский

Endocytosis in cancer and cancer therapy DOI
Blerida Banushi, Shannon R. Joseph, Benedict Lum

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(7), P. 450 - 473

Published: May 22, 2023

Language: Английский

Citations

97
Response of cells and tissues to shear stress DOI Creative Commons
Jaime A. Espina, Marília H. Cordeiro, Milan Milivojević

et al.

Journal of Cell Science, Journal Year: 2023, Volume and Issue: 136(18)

Published: Sept. 15, 2023

ABSTRACT Shear stress is essential for normal physiology and malignancy. Common physiological processes – such as blood flow, particle flow in the gut, or contact between migratory cell clusters their substrate produce shear that can have an impact on behavior of different tissues. In addition, has roles biomedical interest, wound healing, cancer fibrosis induced by soft implants. Thus, understanding how cells react adapt to important. this Review, we discuss vivo vitro data obtained from vascular epithelial models; highlight insights these afforded regarding general mechanisms through which sense, transduce respond at cellular levels; outline changes experience response tissue organization. Finally, role collective migration, only starting be appreciated. We review our current effects context embryo development, fibrosis, invite scientific community further investigate scenarios.

Language: Английский

Citations

51
MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation DOI

Weiwei Ren,

Rebeca Kawahara, Kenichi Suzuki

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(3)

Published: Jan. 3, 2025

Many cancer cells exhibit increased amounts of paucimannose glycans, which are truncated N-glycan structures rarely found in mammals. Paucimannosidic proteins proposedly generated within lysosomes and exposed on the cell surface through a yet uncertain mechanism. In this study, we revealed that paucimannosidic produced by lysosomal glycosidases secreted via exocytosis. Interestingly, exocytosis preferentially occurred vicinity focal adhesions, protein complexes connecting actin cytoskeleton to extracellular matrix. Through genome-wide knockout screening, identified MYO18B, an crosslinker, is required for adhesion maturation, facilitating release milieu. Moreover, mechanosensitive cation channel PIEZO1 locally activated at adhesions imports Ca2+ necessary lysosome-plasma membrane fusion. Collectively, our study unveiled intimate relationship between adhesion, shedding light unexpected interplay activities cellular mechanosensing.

Language: Английский

Citations

4
Thy-1 (CD90)-regulated cell adhesion and migration of mesenchymal cells: insights into adhesomes, mechanical forces, and signaling pathways DOI Creative Commons
Alejandra Valdivia,

Ana M. Avalos,

Lisette Leyton

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Nov. 30, 2023

Cell adhesion and migration depend on the assembly disassembly of adhesive structures known as focal adhesions. Cells adhere to extracellular matrix (ECM) form these via receptors, such integrins syndecans, which initiate signal transduction pathways that bridge ECM cytoskeleton, thus governing processes. Integrins bind soluble or cell surface ligands integrin complexes (IAC), whose composition depends cellular context type. Proteomic analyses IACs led curation term adhesome, is a complex molecular network containing hundreds proteins involved in signaling, adhesion, movement. One hallmarks sense mechanical cues arise due rigidity, well tension exerted by cell-cell interactions, transduce this force modifying actin cytoskeleton regulate migration. Among integrin/syndecan ligands, we have described Thy-1 (CD90), GPI-anchored protein possesses binding domains for each receptors and, upon engaging them, stimulates In review, examine what currently about adhesomes, revise how forces changed our view regulation migration, context, discuss contributed understanding signaling mechanisms control

Language: Английский

Citations

14
Finite Element Modeling of Cells Adhering to a Substrate: An Overview DOI Creative Commons
Lorenzo Santoro, Lorenzo Vaiani, Antonio Boccaccio

et al.

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 2596 - 2596

Published: March 20, 2024

In tissue formation and regeneration processes, cells often move collectively, maintaining connections through intercellular adhesions. However, the specific roles of cell–substrate cell-to-cell mechanical interactions in regulation collective cell migration are not yet fully understood. Finite element modeling (FEM) may be a way to assess more deeply biological, mechanical, chemical phenomena behind adhesion. FEM is powerful tool widely used simulate described by systems partial differential equations. For example, provides information on stress/strain state adhering substrate, as well its mechanobiological behavior. This review paper, after briefly describing basic principles adhesion, surveys most important studies that have utilized investigate structural response substrate how forces acting adhesive structures affect global

Language: Английский

Citations

4
Deciphering the dynamics: Exploring the impact of mechanical forces on histone acetylation DOI
Jingyi Cai, Yudi Deng, Ziyang Min

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(15)

Published: Aug. 3, 2024

Abstract Living cells navigate a complex landscape of mechanical cues that influence their behavior and fate, originating from both internal external sources. At the molecular level, translation these physical stimuli into cellular responses relies on intricate coordination mechanosensors transducers, ultimately impacting chromatin compaction gene expression. Notably, epigenetic modifications histone tails govern accessibility gene‐regulatory sites, thereby regulating Among modifications, acetylation emerges as particularly responsive to microenvironment, exerting significant control over activities. However, precise role in mechanosensing transduction remains elusive due complexity network. To address this gap, our aim is systematically explore key regulators multifaceted roles response biomechanical stimuli. In review, we initially introduce ubiquitous force experienced by then dynamic alterations its associated co‐factors, including HDACs, HATs, acetyl‐CoA, cues. Furthermore, delve interactions between mechanosensors/mechanotransducers, offering comprehensive analysis. Ultimately, review aims provide holistic understanding nuanced interplay forces within an academic framework.

Language: Английский

Citations

4
Coordination of Focal Adhesion Nanoarchitecture and Dynamics in Mechanosensing for Cardiomyoblast Differentiation DOI Creative Commons
Jingwei Xiao, Jing Wen Ang,

Xueying Zhong

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Focal adhesions (FAs) are force-bearing multiprotein complexes, whose nanoscale organization and signaling essential for cell growth differentiation. However, the specific of FA components to exert spatiotemporal activation proteins force sensing transduction remains unclear. In this study, we unveil intricacies protein nanoarchitecture that its dynamics coordinated by a molecular scaffold protein, BNIP-2, initiate downstream signal cardiomyoblast Within FAs, BNIP-2 regulates nano-organization focal adhesion kinase (FAK), FAK, paxillin, vinculin. Depletion resulted in altered numbers sizes per cell, reduced traction force, decreased sensitivity mechanosensing. At level, loss disrupted FAK-paxillin axis, where FAK inhibition reproduces effects impairing phosphorylation both paxillin. Mechanistically, preferentially binds constitutively active acts as mediate interactions between paxillin We have validated BNIP-2's role axis human embryonic stem cells (hESC). Furthermore, showed depletion changes signature gene targets at cardiac progenitor stage summary, intricate interplay dynamics, governed is crucial biochemical driving

Language: Английский

Citations

0
Collagen Fiber Density Observed in Metastatic Ovarian Cancer Promotes Tumor Cell Adhesion DOI
Ali Abbaspour,

Ana Cavazos,

Roshan M. Patel

et al.

Published: Jan. 1, 2025

Collagen type I, a key structural component of the extracellular matrix (ECM), is frequently altered in cancer, with fiber organization at primary tumor site linked to metastasis and poor patient outcomes. Here, we demonstrate that collagen fibers are also metastatic sites such as omentum patients high-grade serous ovarian cancer (HGSOC). Specifically, observed significant increase density, alignment, width. To determine if these changes support metastasis, used semi-interpenetrating methacrylated gelatin (gelMA) network combination fibrillar or gelatin. Cancer cells had significantly increased adhesion spreading on gelMA fibers. Cells similar polyethylene glycol (PEG) scaffolds modified RGD (gelatin peptide) RGD+GFOGER (collagen peptide), while PCL-gelatin compared flat substrates. These results suggested cell resulted from structure itself. We investigated mechanism responsible for this effect found actin polymerization, but not myosin II contractility, was needed adhesion. further demonstrated fibrous gels more robust greater strength. suggest will development additional metastases.

Language: Английский

Citations

0
Vitronectin Regulates Focal Adhesion Turnover and Migration of Human Placenta-derived MSCs under Nutrient Stress DOI Creative Commons

Srishti Dutta Gupta,

Nitish Pal,

Malancha Ta

et al.

European Journal of Cell Biology, Journal Year: 2025, Volume and Issue: unknown, P. 151477 - 151477

Published: Jan. 1, 2025

Language: Английский

Citations

0
Mitsugumin 53 Inhibits Angiogenesis Through Regulating Focal Adhesion Turnover and Tip Cell Formation DOI Creative Commons

Shuangshuang Yuan,

Yu Qin, Tangting Chen

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(4)

Published: Feb. 1, 2025

ABSTRACT Our previous studies have identified mitsugumin 53 (MG53) as a novel regulator for angiogenesis by directly entering endothelial cells and modulating focal adhesion kinase (FAK) activation, but little is known about how rhMG53 taken up mediates cell movement. In the present study, we demonstrated that knockdown of caveolin‐1 clathrin inhibitor, pitstop‐2, both significantly reduced entry into cells, indicating caveolae‐dependent clathrin‐dependent endocytosis during this process. The internalised remarkably inhibited phosphorylation FAK downstream signalling molecule paxillin, consequently resulting in significant decrease turnover spreading migration. Using 3D collagen culture model, further found tip formation tubulogenesis. Furthermore, also prevented alkaline injury‐induced corneal neovascularization vivo. Taken together, these results indicate inhibits through regulating formation. This may elucidate molecular mechanisms involved uptake rhMG53‐modulated function provide evidence potential utility treating diseases with excessive angiogenesis.

Language: Английский

Citations

0