ArticleDisease models & mechanisms
Loss of fibulin-5 binding to beta1 integrins inhibits tumor growth by increasing the level of ROS.
Article in Disease models & mechanisms. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- Integrin-Binding Matricellular Protein Fibulin-5 Maintains Epidermal Stem Cell Heterogeneity During Skin Aging.Aging cell · 2026Article
- The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner.iScience · 2025Article
- Does each Component of Reactive Oxygen Species have a Dual Role in the Tumor Microenvironment?Current medicinal chemistry · 2024Review
- Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.British journal of cancer · 2023Article
- Chemical Factory-Guaranteed Enhanced Chemodynamic Therapy for Orthotopic Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Review
- High beta integrin expression is differentially associated with worsened pancreatic ductal adenocarcinoma outcomes.American journal of cancer research · 2022Article
- PCNA inhibition enhances the cytotoxicity of β-lapachone in NQO1-Positive cancer cells by augmentation of oxidative stress-induced DNA damage.Cancer letters · 2021Article
- Effect of fibulin-5 on aldosterone-induced apoptosis in human ascending aortic smooth muscle cells.Experimental and therapeutic medicine · 2021Article
- PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC.Molecular therapy. Nucleic acids · 2021Article
- Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma.Experimental and therapeutic medicine · 2020Article
- lncRNA SLC7A11-AS1 Promotes Chemoresistance by Blocking SCFMolecular therapy. Nucleic acids · 2020Article
- De novo variants in an extracellular matrix protein coding gene, fibulin-5 (FBLN5) are associated with pseudoexfoliation.European journal of human genetics : EJHG · 2019Article
- Mechanisms of weight regain after weight loss - the role of adipose tissue.Nature reviews. Endocrinology · 2019Review
- Dysregulation of fibulin-5 and matrix metalloproteases in epithelial ovarian cancer.Oncotarget · 2018Article
- Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells.Seminars in immunology · 2017Review
- Identification of the matricellular protein Fibulin-5 as a target molecule of glucokinase-mediated calcineurin/NFAT signaling in pancreatic islets.Scientific reports · 2017Article
- Fibulin-4 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition via the PI3K/Akt/mTOR pathway.International journal of oncology · 2017Article
- Hypoxia and Transforming Growth Factor β Cooperate to Induce Fibulin-5 Expression in Pancreatic Cancer.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor survival depends in part on the ability of tumor cells to transform the surrounding extracellular matrix (ECM) into an environment conducive to tumor progression. Matricellular proteins are secreted into the ECM and impact signaling pathways that are required for pro-tumorigenic activities such as angiogenesis. Fibulin-5 (Fbln5) is a matricellular protein that was recently shown to regulate angiogenesis; however, its effect on tumor angiogenesis and thus tumor growth is currently unknown. We report that the growth of pancreatic tumors and tumor angiogenesis is suppressed in Fbln5-null (Fbln5(-/-)) mice compared with wild-type (WT) littermates. Furthermore, we observed an increase in the level of reactive oxygen species (ROS) in tumors grown in Fbln5(-/-) animals. Increased ROS resulted in elevated DNA damage, increased apoptosis of endothelial cells within the tumor, and represented the underlying cause for the reduction in angiogenesis and tumor growth. In vitro, we identified a novel pathway by which Fbln5 controls ROS production through a mechanism that is dependent on beta1 integrins. These results were validated in Fbln5(RGE/RGE) mice, which harbor a point mutation in the integrin-binding RGD motif of Fbln5, preventing its interaction with integrins. Tumor growth and angiogenesis was reduced in Fbln5(RGE/RGE) mice, however treatment with an antioxidant rescued angiogenesis and elevated tumor growth to WT levels. These findings introduce a novel function for Fbln5 in the regulation of integrin-induced ROS production and establish a rationale for future studies to examine whether blocking Fbln5 function could be an effective anti-tumor strategy, alone or in combination with other therapies.
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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.