ArticlePloS one2013
The anti-migratory effects of FKBPL and its peptide derivative, AD-01: regulation of CD44 and the cytoskeletal pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Association of Vascular Endothelial Growth Factors (VEGFs) with Recurrent Miscarriage: A Systematic Review of the Literature.International journal of molecular sciences · 2023Pooled it
- FKBPL: a marker of good prognosis in breast cancer.Oncotarget · 2015Pooled it
- Exendin-4 protects brain endothelial cell damage against hyperammonemic condition.Biochemistry and biophysics reports · 2026Article
- CRISPR/Cas9-mediated gene editing in trophoblast cells via mechanoporation for preeclampsia insight.Cell death & disease · 2025Article
- Multiomics Mendelian randomization integrating pQTL, eQTL and mQTL data revealed BTN3A2 as a potential drug target for nephrolithiasis.Scientific reports · 2025Article
- The FKBPL-based therapeutic peptide, AD-01, protects the endothelium from hypoxia-induced damage by stabilising hypoxia inducible factor-α and inflammation.Journal of translational medicine · 2025Article
- MRI radiomics based on machine learning in high-grade gliomas as a promising tool for prediction of CD44 expression and overall survival.Scientific reports · 2025Article
- Evaluating oxidative stress targeting treatments inFrontiers in cell and developmental biology · 2025Article
- Resolving the current controversy of use and reuse of housekeeping proteins in ageing research: Focus on saving people's tax dollars.Ageing research reviews · 2024Review
- Hsa_circ_0001402 alleviates vascular neointimal hyperplasia through a miR-183-5p-dependent regulation of vascular smooth muscle cell proliferation, migration, and autophagy.Journal of advanced research · 2024Article
- FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility.Biomolecules · 2023Article
- A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.Cellular and molecular life sciences : CMLS · 2023Article
- Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia.Biology of sex differences · 2021Article
- FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.Frontiers in endocrinology · 2021Article
- Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.The Journal of clinical endocrinology and metabolism · 2021Article
- FKBPL is associated with metabolic parameters and is a novel determinant of cardiovascular disease.Scientific reports · 2020Article
- FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer.British journal of cancer · 2020Article
- A Three-DimensionalTissue engineering. Part C, Methods · 2019Article
- FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4.BMC cancer · 2019Article
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
FK506 binding protein-like (FKBPL) and its peptide derivatives exert potent anti-angiogenic activity in vitro and in vivo and control tumour growth in xenograft models, when administered exogenously. However, the role of endogenous FKBPL in angiogenesis is not well characterised. Here we investigated the molecular effects of the endogenous protein and its peptide derivative, AD-01, leading to their anti-migratory activity. Inhibition of secreted FKBPL using a blocking antibody or siRNA-mediated knockdown of FKBPL accelerated the migration of human microvascular endothelial cells (HMEC-1). Furthermore, MDA-MB-231 tumour cells stably overexpressing FKBPL inhibited tumour vascular development in vivo suggesting that FKBPL secreted from tumour cells could inhibit angiogenesis. Whilst FKBPL and AD-01 target CD44, the nature of this interaction is not known and here we have further interrogated this aspect. We have demonstrated that FKBPL and AD-01 bind to the CD44 receptor and inhibit tumour cell migration in a CD44 dependant manner; CD44 knockdown abrogated AD-01 binding as well as its anti-migratory activity. Interestingly, FKBPL overexpression and knockdown or treatment with AD-01, regulated CD44 expression, suggesting a co-regulatory pathway for these two proteins. Downstream of CD44, alterations in the actin cytoskeleton, indicated by intense cortical actin staining and a lack of cell spreading and communication were observed following treatment with AD-01, explaining the anti-migratory phenotype. Concomitantly, AD-01 inhibited Rac-1 activity, up-regulated RhoA and the actin binding proteins, profilin and vinculin. Thus the anti-angiogenic protein, FKBPL, and AD-01, offer a promising and alternative approach for targeting both CD44 positive tumours and vasculature networks.
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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.