ArticleThe Journal of biological chemistry2012
Endorepellin affects angiogenesis by antagonizing diverse vascular endothelial growth factor receptor 2 (VEGFR2)-evoked signaling pathways: transcriptional repression of hypoxia-inducible factor 1α and VEGFA and concurrent inhibition of nuclear factor of activated T cell 1 (NFAT1) activation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 73 citations in OpenAlex.
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- An endothelial-related prognostic index for bladder cancer patients.Discover oncology · 2024Article
- Global impact of proteoglycan science on human diseases.iScience · 2023Review
- Identification of endothelial-related molecular subtypes for bladder cancer patients.Frontiers in oncology · 2023Article
- Neuroinflammation aggravated by traumatic brain injury at high altitude is reversed by L-serineFrontiers in cellular neuroscience · 2023Article
- Suppression of PI3K signaling is linked to autophagy activation and the spatiotemporal induction of the lens organelle free zone.Experimental cell research · 2022Article
- Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways.American journal of physiology. Cell physiology · 2022Review
- Extracellular matrix guidance of autophagy: a mechanism regulating cancer growth.Open biology · 2022Review
- A functional outside-in signaling network of proteoglycans and matrix molecules regulating autophagy.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Angiostatic cues from the matrix: Endothelial cell autophagy meets hyaluronan biology.The Journal of biological chemistry · 2020Review
- Proteoglycan-driven Autophagy: A Nutrient-independent Mechanism to Control Intracellular Catabolism.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Review
- Role of Extracellular Matrix in Gastrointestinal Cancer-Associated Angiogenesis.International journal of molecular sciences · 2020Review
- Endorepellin evokes an angiostatic stress signaling cascade in endothelial cells.The Journal of biological chemistry · 2020Article
- Proteoglycan signaling in tumor angiogenesis and endothelial cell autophagy.Seminars in cancer biology · 2020Review
- Catabolic degradation of endothelial VEGFA via autophagy.The Journal of biological chemistry · 2020Article
- Tumor necrosis factor receptor-2 signaling pathways promote survival of cancer stem-like CD133FASEB bioAdvances · 2020Article
- Identification of the Six-RNA-Binding Protein Signature for Prognosis Prediction in Bladder Cancer.Frontiers in genetics · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Endorepellin, the angiostatic C-terminal domain of the heparan sulfate proteoglycan perlecan, inhibits angiogenesis by simultaneously binding to the α2β1 integrin and the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) on endothelial cells. This interaction triggers the down-regulation of both receptors and the concurrent activation of the tyrosine phosphatase SHP-1, which leads to a signaling cascade resulting in angiostasis. Here, we provide evidence that endorepellin is capable of attenuating both the PI3K/PDK1/Akt/mTOR and the PKC/JNK/AP1 pathways. We show that hypoxia-inducible factor 1α (HIF-1α) transcriptional activity induced by VEGFA was inhibited by endorepellin independent of oxygen concentration and that only a combination of both PI3K and calcineurin inhibitors completely blocked the suppressive activity evoked by endorepellin on HIF1A and VEGFA promoter activity. Moreover, endorepellin inhibited the PKC/JNK/AP1 axis induced by the recruitment of phospholipase γ and attenuated the VEGFA-induced activation of NFAT1, a process dependent on calcineurin activity. Finally, endorepellin inhibited VEGFA-evoked nuclear translocation of NFAT1 and promoted NFAT1 stability. Thus, we provide evidence for a novel downstream signaling axis for an angiostatic fragment and for the key components involved in the dual antagonistic activity of endorepellin, highlighting its potential use as a therapeutic agent.
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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.