ArticleThe Journal of biological chemistry2013
Lactate engages receptor tyrosine kinases Axl, Tie2, and vascular endothelial growth factor receptor 2 to activate phosphoinositide 3-kinase/Akt and promote angiogenesis.
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 94 papers.
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Who cites it
94 citing papers in PubMed, 170 citations in OpenAlex.
- Angiocrine factors in tumor microenvironment: bidirectional crosstalk, mechanistic insights, and therapeutic strategies.Journal of translational medicine · 2026Review
- Beyond a waste product: lactate as a master metabolite dictating anti-tumor T-cell fate.Cell death & disease · 2026Review
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Lactate metabolism and lactylation: Therapeutic and pre-clinical implications in neovascularization in peripheral artery disease.Journal of pharmaceutical analysis · 2026Review
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
- Beyond cartilage degeneration: osteoarthritis as a systems failure of inflammation regulation.Frontiers in medicine · 2026Article
- Metabolic Symbiosis Between Cancer Cells and Endothelial Cells: A Key Driver of Tumor Angiogenesis.Advances in experimental medicine and biology · 2026Review
- Metabolic Reprogramming and Cell Interaction in Atherosclerosis: From Molecular Mechanisms to Therapeutic Strategies.Journal of cardiovascular development and disease · 2025Review
- Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies.Biomarker research · 2025Review
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Physical activity and glioblastoma: a paradigm shift in neuro-oncology therapy.Frontiers in oncology · 2025Review
- AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.Experimental hematology & oncology · 2024Review
- Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer.Cancer research · 2024Article
- Aerobic glycolysis of vascular endothelial cells: a novel perspective in cancer therapy.Molecular biology reports · 2024Review
- GAS6/TAM Axis as Therapeutic Target in Liver Diseases.Seminars in liver disease · 2024Article
- Targeting hypoxia signaling pathways in angiogenesis.Frontiers in physiology · 2024Review
- Tumor-Associated Macrophage Targeting of Nanomedicines in Cancer Therapy.Pharmaceutics · 2023Review
- Concurrent induction of apoptosis and necroptosis in apigenin‑treated malignant mesothelioma cells: Reversal of Warburg effect through Akt inhibition and p53 upregulation.Oncology reports · 2023Article
- Metabolic reprogramming of the ovarian cancer microenvironment in the development of antiangiogenic resistance.Acta biochimica et biophysica Sinica · 2023Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Although a high level of lactate is quintessential to both tumors and wound healing, the manner by which lactate impacts endothelial cells to promote angiogenesis and thereby create or restore vascular perfusion to growing tissues has not been fully elucidated. Here we report that lactate activated the PI3K/Akt pathway in primary human endothelial cells. Furthermore, activating this signaling pathway was required for lactate-stimulated organization of endothelial cells into tubes and for sprouting of vessels from mouse aortic explants. Lactate engaged the PI3K/Akt pathway via ligand-mediated activation of the three receptor tyrosine kinases Axl, Tie2, and VEGF receptor 2. Neutralizing the ligands for these receptor tyrosine kinases, pharmacologically inhibiting their kinase activity or suppressing their expression largely eliminated the ability of cells and explants to respond to lactate. Elucidating the mechanism by which lactate communicates with endothelial cells presents a previously unappreciated opportunity to improve our understanding of the angiogenic program and to govern it.
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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.