ArticleThe Journal of biological chemistry2013
Netrin-1 promotes glioblastoma cell invasiveness and angiogenesis by multiple pathways including activation of RhoA, cathepsin B, and cAMP-response element-binding protein.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Systematic review of protein biomarkers of invasive behavior in glioblastoma.Molecular neurobiology · 2014Pooled it
- Cathepsin B in urological tumors: unraveling its role and therapeutic potential.Discover oncology · 2025Review
- Brain-derived endothelial cells are neuroprotective in a chronic cerebral hypoperfusion mouse model.Communications biology · 2024Article
- Involvement of neuronal factors in tumor angiogenesis and the shaping of the cancer microenvironment.Frontiers in immunology · 2024Review
- The role and clinical relevance of long non-coding RNAs in glioma.Non-coding RNA research · 2023Article
- Disease specific urinary biomarkers in the central nervous system.Scientific reports · 2023Article
- ZNF133 is a potent suppressor in breast carcinogenesis through dampening L1CAM, a driver for tumor progression.Oncogene · 2023Article
- The Role of Cathepsin B in Pathophysiologies of Non-tumor and Tumor tissues: A Systematic Review.Journal of Cancer · 2023Review
- The role of lysosomal peptidases in glioma immune escape: underlying mechanisms and therapeutic strategies.Frontiers in immunology · 2023Review
- Netrin-1 Stimulates Migration of Neogenin Expressing Aggressive Melanoma Cells.International journal of molecular sciences · 2022Article
- Inactivation of axon guidance molecule netrin-1 in human colorectal cancer by an epigenetic mechanism.Biochemical and biophysical research communications · 2022Article
- NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer.Scientific reports · 2022Article
- Article
- Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma.Neuro-oncology · 2021Article
- Netrin-1 in Glioblastoma Neovascularization: The New Partner in Crime?International journal of molecular sciences · 2021Review
- Transcriptomics-Based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma Cells.Cancers · 2021Article
- T-Cell Immunotherapy for Pediatric High-Grade Gliomas: New Insights to Overcoming Therapeutic Challenges.Frontiers in oncology · 2021Review
- Cathepsin B is highly expressed in pancreatic cancer stem-like cells and is associated with patients' surgical outcomes.Oncology letters · 2021Article
- Recent Trends of microRNA Significance in Pediatric Population Glioblastoma and Current Knowledge of Micro RNA Function in Glioblastoma Multiforme.International journal of molecular sciences · 2020Review
- Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
Glioblastomas are very difficult tumors to treat because they are highly invasive and disseminate within the normal brain, resulting in newly growing tumors. We have identified netrin-1 as a molecule that promotes glioblastoma invasiveness. As evidence, netrin-1 stimulates glioblastoma cell invasion directly through Matrigel-coated transwells, promotes tumor cell sprouting and enhances metastasis to lymph nodes in vivo. Furthermore, netrin-1 regulates angiogenesis as shown in specific angiogenesis assays such as enhanced capillary endothelial cells (EC) sprouting and by increased EC infiltration into Matrigel plugs in vivo, as does VEGF-A. This netrin-1 signaling pathway in glioblastoma cells includes activation of RhoA and cyclic AMP response element-binding protein (CREB). A novel finding is that netrin-1-induced glioblastoma invasiveness and angiogenesis are mediated by activated cathepsin B (CatB), a cysteine protease that translocates to the cell surface as an active enzyme and co-localizes with cell surface annexin A2 (ANXA2). The specific CatB inhibitor CA-074Me inhibits netrin-1-induced cell invasion, sprouting, and Matrigel plug angiogenesis. Silencing of CREB suppresses netrin-1-induced glioblastoma cell invasion, sprouting, and CatB expression. It is concluded that netrin-1 plays an important dual role in glioblastoma progression by promoting both glioblastoma cell invasiveness and angiogenesis in a RhoA-, CREB-, and CatB-dependent manner. Targeting netrin-1 pathways may be a promising strategy for brain cancer therapy.
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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.