ArticleBiomedicines2021
Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment.
Article in Biomedicines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- More than a ring: the emerging role of heme in angiogenesis.Cell communication and signaling : CCS · 2026Review
- Comprehensive bioinformatics and experimental analysis of PPOX reveals its carcinogenic effect in clear cell renal cell carcinoma.Translational andrology and urology · 2026Article
- An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA.Blood · 2025Article
- Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.Cell reports. Medicine · 2024Article
- Unearthing FLVCR1a: tracing the path to a vital cellular transporter.Cellular and molecular life sciences : CMLS · 2024Review
- FLVCR1a Controls Cellular Cholesterol Levels through the Regulation of Heme Biosynthesis and Tricarboxylic Acid Cycle Flux in Endothelial Cells.Biomolecules · 2024Article
- Endothelial cells require functional FLVCR1a during developmental and adult angiogenesis.Angiogenesis · 2023Article
- Review
- The promise of targeting heme and mitochondrial respiration in normalizing tumor microenvironment and potentiating immunotherapy.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth. In addition to their angiogenic properties, tumor-associated ECs (TECs) establish a unique vascular niche that actively modulates cancer development by shuttling a selected pattern of factors and metabolites to the CC. The profile of secreted metabolites is strictly dependent on the metabolic status of the cell, which is markedly perturbed in TECs. Recent evidence highlights the involvement of heme metabolism in the regulation of energy metabolism in TECs. The present study shows that interfering with endothelial heme metabolism by targeting the cell membrane heme exporter Feline Leukemia Virus subgroup C Receptor 1a (FLVCR1a) in TECs, resulted in enhanced fatty acid oxidation (FAO). Moreover, FAO-derived acetyl-CoA was partly consumed through ketogenesis, resulting in ketone bodies (KBs) accumulation in FLVCR1a-deficient TECs. Finally, the results from this study also demonstrate that TECs-derived KBs can be secreted in the extracellular environment, inducing a metabolic rewiring in the CC. Taken together, these data may contribute to finding new metabolic vulnerabilities for 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.