| First Author | Pi J | Year | 2024 |
| Journal | Redox Biol | Volume | 75 |
| Pages | 103281 | PubMed ID | 39083899 |
| Mgi Jnum | J:359003 | Mgi Id | MGI:7713871 |
| Doi | 10.1016/j.redox.2024.103281 | Citation | Pi J, et al. (2024) Therapeutic efficacy of ECs Foxp1 targeting Hif1alpha-Hk2 glycolysis signal to restrict angiogenesis. Redox Biol 75:103281 |
| abstractText | Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and the normalization of hyperglycolysis in tumor vessels has recently gained attention as a therapeutic target. We analyzed the TCGA database and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated reduced expression more restricted at tumor vascular ECs. Therefore, we investigated the function and mechanisms of Foxp1 in EC metabolism for tumor angiogenesis required for tumor growth. EC-Foxp1 deletion mice exhibited a significant increase of tumor and retinal developmental angiogenesis and Hif1alpha was identified as Foxp1 target gene, and Hk2 as Hif1alpha target gene. The Foxp1-Hif1alpha-Hk2 pathway in ECs is important in the regulation of glycolytic metabolism to govern tumor angiogenesis. Finally, we used genetic deletion of EC-Hif1alpha and RGD-peptide nanoparticles EC target delivery of Hif1alpha/Hk2-siRNAs to knockdown gene expression which reduced the tumor EC hyperglycolysis state and restricted angiogenesis for tumor growth. This study advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth. |
