ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Matrix stiffness regulates vascular integrity through focal adhesion kinase activity.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 77 citations in OpenAlex.
- Active Microrheology Reveals Distinct ECM Mechanical Signatures Induced by Stromal Cells of Different Tissue Origins during Vascular Morphogenesis.ACS biomaterials science & engineering · 2026Article
- Mechanobiology of solid tumor vasculature: implications for tumor progression.Cancer metastasis reviews · 2026Review
- The Synthetic Extracellular Matrix as a Maestro of the In Vitro Stem Cell Niche: Orchestrating Fate and Function.Biomedicines · 2026Review
- Cancer cells metastasize in several types of cancer via two distinct routes, probably based on mechanical signals.Frontiers in cell and developmental biology · 2026Review
- Mechanosensitive biochemical imprinting of the talin interaction with DLC1 regulates RhoA activity and cardiomyocyte remodeling.Science advances · 2025Article
- Diabetic hyperglycemia-induced glycation regulates tumor vasculature integrity via NF-κB-mediated GM-CSF secretion by tumor cells.Cell biomaterials · 2025Article
- Biomechanics of the tumor extracellular matrix and regulatory T cells: regulatory mechanisms and potential therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Mechanical regulation of extracellular vesicle activity during tumour progression.Nature biomedical engineering · 2025Review
- Review
- Matrix Stiffness-Mediated DNA Methylation in Endothelial Cells.Cellular and molecular bioengineering · 2025Article
- Research progress on the role of biomechanical clues in the progression of lung cancer.Frontiers in cell and developmental biology · 2025Review
- Junctions at the crossroads: the impact of mechanical cues on endothelial cell-cell junction conformations and vascular permeability.American journal of physiology. Cell physiology · 2024Review
- Biomaterial systems for evaluating the influence of ECM mechanics on anti-fibrotic therapeutic efficacy.Matrix biology plus · 2024Article
- c-Src-induced vascular malformations require localised matrix degradation at focal adhesions.Journal of cell science · 2024Article
- Glycogen synthase kinase 3 activity enhances liver inflammation in MASH.JHEP reports : innovation in hepatology · 2024Article
- Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease.The Journal of clinical investigation · 2024Article
- A Hierarchical Mechanotransduction System: From Macro to Micro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- [Protective effect of FAK inhibitor PF-562271 against human umbilical vein endothelial cell injury induced by aging platelets].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- [Research Progress on the Influence of Tumor Extracellular Matrix Mechanic Properties on Nanodrug Delivery].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.Nature communications · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor vasculature is known to be more permeable than the vasculature found in healthy tissue, which in turn can lead to a more aggressive tumor phenotype and impair drug delivery into tumors. While the stiffening of the stroma surrounding solid tumors has been reported to increase vascular permeability, the mechanism of this process remains unclear. Here, we utilize an in vitro model of tumor stiffening, ex ovo culture, and a mouse model to investigate the molecular mechanism by which matrix stiffening alters endothelial barrier function. Our data indicate that the increased endothelial permeability caused by heightened matrix stiffness can be prevented by pharmaceutical inhibition of focal adhesion kinase (FAK) both in vitro and ex ovo. Matrix stiffness-mediated FAK activation determines Src localization to cell-cell junctions, which then induces increased vascular endothelial cadherin phosphorylation both in vitro and in vivo. Endothelial cells in stiff tumors have more activated Src and higher levels of phosphorylated vascular endothelial cadherin at adherens junctions compared to endothelial cells in more compliant tumors. Altogether, our data indicate that matrix stiffness regulates endothelial barrier integrity through FAK activity, providing one mechanism by which extracellular matrix stiffness regulates endothelial barrier function. Additionally, our work also provides further evidence that FAK is a promising potential target for cancer therapy because FAK plays a critical role in the regulation of endothelial barrier integrity.-Wang, W., Lollis, E. M., Bordeleau, F., Reinhart-King, C. A. Matrix stiffness regulates vascular integrity through focal adhesion kinase activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.