ArticleAmerican journal of cancer research2020
Integrin αVβ5/Akt/Sp1 pathway participates in matrix stiffness-mediated effects on VEGFR2 upregulation in vascular endothelial cells.
Article in American journal of cancer research, 2020. 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, 16 citations in OpenAlex.
- Mechanobiology of solid tumor vasculature: implications for tumor progression.Cancer metastasis reviews · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Extracellular matrix in vascular homeostasis and disease.Nature reviews. Cardiology · 2025Review
- Angiogenesis within atherosclerotic plaques: Mechanical regulation, molecular mechanism and clinical diagnosis.Mechanobiology in medicine · 2025Review
- A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma.Nature communications · 2025Article
- Unveiling the potential of biomechanics in pioneering innovative strategies for cancer therapy.Theranostics · 2025Review
- Complement factor H in molecular regulation of angiogenesis.Medical review (2021) · 2024Review
- A Hierarchical Mechanotransduction System: From Macro to Micro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- RGDSP-functionalized peptide hydrogel stimulates growth factor secretion via integrin αv/PI3K/AKT axis for improved wound healing by human amniotic mesenchymal stem cells.Frontiers in bioengineering and biotechnology · 2024Article
- Matrix stiffness-driven cancer progression and the targeted therapeutic strategy.Mechanobiology in medicine · 2023Review
- [Research progress of matrix stiffness in regulating endothelial cell sprouting].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2023Review
- Adjusting the stiffness of a cell-free hydrogel system based on tissue-specific extracellular matrix to optimize adipose tissue regeneration.Burns & trauma · 2023Article
- Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer.Cell death & disease · 2022Article
- Activation of Piezo1 contributes to matrix stiffness-induced angiogenesis in hepatocellular carcinoma.Cancer communications (London, England) · 2022Article
- UBAP2L promotes gastric cancer metastasis by activating NF-κB through PI3K/AKT pathway.Cell death discovery · 2022Article
- FAK Regulates VEGFR2 Expression and Promotes Angiogenesis in Triple-Negative Breast Cancer.Biomedicines · 2021Article
- Expression and Pathogenic Analysis of Integrin Family Genes in Systemic Sclerosis.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous study has validated that higher matrix stiffness obviously improves vascular endothelial growth factor (VEGF) expression in HCC cells, highlighting a linkage between matrix stiffness and HCC angiogenesis. However, the effects of matrix stiffness on vascular endothelial cells in HCC and its underlying mechanism remain largely uncharacterized. Here we further analyzed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in human umbilical vein endothelial cells (HUVECs) grown on different stiffness substrates and explored its regulatory mechanism for better understanding matrix stiffness-regulated angiogenesis in HCC. Our results revealed that increased matrix stiffness significantly upregulated the expression of VEGFR2 in HUVECs, and the expression level of VEGFR2 was positively correlated with the expression levels of COL1 and lysyl oxidase in human HCC tissues and rat HCC tissue, moreover VEGFR2 and CD34 were co-localized at blood vessel of HCC tissues, indicating an obvious regulation role of matrix stiffness in VEGFR2 expression. Simultaneously, increased matrix stiffness also elevated the phosphorylation level of Akt and the expressions of integrin αV/β5 and nuclear Sp1 in HUVECs. Inhibition of integrin αVβ5 remarkably reversed the expression of VEGFR2 and phosphorylation level of Akt in HUVECs grown on higher stiffness substrate. Except that, PI3K inhibitor also suppressed the phosphorylation level of Akt and the expressions of VEGFR2 and nuclear Sp1 evidently. Taken together, higher matrix stiffness increased VEGFR2 expression in HUVECs, and integrin αVβ5/Akt/Sp1 pathway participated in stiffness-mediated effects on VEGFR2 upregulation. This study combining with our previous report discloses a new paradigm in which higher matrix stiffness as an initiator drives HCC angiogenesis via upregulating both VEGFR2 expression in vascular endothelial cells and VEGF expression in HCC cells.
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Registered trials
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