ArticleBiochemical and biophysical research communications2022
Substrate stiffening promotes VEGF-A functions via the PI3K/Akt/mTOR pathway.
Article in Biochemical and biophysical research communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
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- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
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- Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights into Disease Progression and Therapeutic Targets.Biomedicines · 2023Review
- Glomerular mTORC1 activation was associated with podocytes to endothelial cells communication in lupus nephritis.Lupus science & medicine · 2023Article
- ZD6474 attenuates TGF-β1-induced fibrosis in human Tenon fibroblasts and inhibits neovascularization via AKT-mTOR signaling pathway.International ophthalmology · 2023Article
- Molecular Design, Spectroscopic, DFT, Pharmacological, and Molecular Docking Studies of Novel Ruthenium(III)-Schiff Base Complex: An Inhibitor of Progression in HepG2 Cells.International journal of environmental research and public health · 2022Article
- Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway.Bioengineered · 2022Article
- mTOR Signaling Components in Tumor Mechanobiology.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR signaling pathway. This pathway is activated on stiffer substrates, is amplified by VEGF-A stimulation, and correlates with enhanced endothelial cell (EC) proliferation, contraction, pro-angiogenic secretion, and capillary-like tube formation. In the settings of advanced age-related macular degeneration, characterized by EC and retinal pigment epithelial (RPE)-mediated angiogenesis, these data implicate substrate stiffness as a novel causative mechanism and Akt/mTOR inhibition as a novel therapeutic pathway.
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Registered trials
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