ArticleThe Journal of biological chemistry2016
Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Unwinding the Neurovascular Unit: The Vascular Extracellular Matrix and Mechanochemical Collagen Functionalization in Vascular Dementia.International journal of molecular sciences · 2026Review
- Inhibiting the Secreted RGDKGE Collagen Peptide Selectively Controls CD8The American journal of pathology · 2026Article
- A recombinant humanized type III collagen coating with anti-inflammatory and endothelialization-promoting effects for left atrial appendage closure devices.Regenerative biomaterials · 2026Article
- New Horizons in Cancer Progression and Metastasis:Biomedicines · 2024Review
- Fibroblast Yap/Taz Signaling in Extracellular Matrix Homeostasis and Tissue Fibrosis.Journal of clinical medicine · 2024Review
- Bioengineering liver tissue by repopulation of decellularised scaffolds.World journal of hepatology · 2023Review
- Targeting the secreted RGDKGE collagen fragment reduces PD‑L1 by a proteasome‑dependent mechanism and inhibits tumor growth.Oncology reports · 2023Article
- YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis through Activating YAP Signaling in Vascular Endothelial Cells.Analytical cellular pathology (Amsterdam) · 2022Article
- An RGDKGE-Containing Cryptic Collagen Fragment Regulates Phosphorylation of Large Tumor Suppressor Kinase-1 and Controls Ovarian Tumor Growth by a Yes-Associated Protein-Dependent Mechanism.The American journal of pathology · 2021Article
- Collagen Structure-Function Mapping Informs Applications for Regenerative Medicine.Bioengineering (Basel, Switzerland) · 2020Review
- Cryptic collagen elements as signaling hubs in the regulation of tumor growth and metastasis.Journal of cellular physiology · 2020Review
- Article
- Retinal blood vessel-origin yes-associated protein (YAP) governs astrocytic maturation via leukaemia inhibitory factor (LIF).Cell proliferation · 2020Article
- Effects of age-dependent changes in cell size on endothelial cell proliferation and senescence through YAP1.Aging · 2019Article
- Current progress in the inflammatory background of angiogenesis in gynecological cancers.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- SRC tyrosine kinase activates the YAP/TAZ axis and thereby drives tumor growth and metastasis.The Journal of biological chemistry · 2019Article
- The HU177 Collagen Epitope Controls Melanoma Cell Migration and Experimental Metastasis by a CDK5/YAP-Dependent Mechanism.The American journal of pathology · 2018Article
- Review
- MMP proteolytic activity regulates cancer invasiveness by modulating integrins.Scientific reports · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular matrix (ECM) remodeling regulates angiogenesis. However, the precise mechanisms by which structural changes in ECM proteins contribute to angiogenesis are not fully understood. Integrins are molecules with the ability to detect compositional and structural changes within the ECM and integrate this information into a network of signaling circuits that coordinate context-dependent cell behavior. The role of integrin αvβ3 in angiogenesis is complex, as evidence exists for both positive and negative functions. The precise downstream signaling events initiated by αvβ3 may depend on the molecular characteristics of its ligands. Here, we identified an RGD-containing cryptic collagen epitope that is generated in vivo. Surprisingly, rather than inhibiting αvβ3 signaling, this collagen epitope promoted αvβ3 activation and stimulated angiogenesis and inflammation. An antibody directed to this RGDKGE epitope but not other RGD collagen epitopes inhibited angiogenesis and inflammation in vivo. The selective ability of this RGD epitope to promote angiogenesis and inflammation depends in part on its flanking KGE motif. Interestingly, a subset of macrophages may represent a physiologically relevant source of this collagen epitope. Here, we define an endothelial cell mechano-signaling pathway in which a cryptic collagen epitope activates αvβ3 leading to an Src and p38 MAPK-dependent cascade that leads to nuclear accumulation of Yes-associated protein (YAP) and stimulation of endothelial cell growth. Collectively, our findings not only provide evidence for a novel mechano-signaling pathway, but also define a possible therapeutic strategy to control αvβ3 signaling by targeting a pro-angiogenic and inflammatory ligand of αvβ3 rather than the receptor itself.
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Registered trials
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.