ArticleScientific reports2017
Hypoxia-induced angiotensin II by the lactate-chymase-dependent mechanism mediates radioresistance of hypoxic tumor cells.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- A systematic review of the measurement of the renin-angiotensin and kallikrein-kinin system peptides in normotension and hypertension.Journal of human hypertension · 2026Pooled it
- A pharmacodynamic study of rapid lactate metabolic modulation by intravenous L-arginine in brain metastases.Frontiers in oncology · 2026Trial
- Drug Repurposing to Circumvent Immune Checkpoint Inhibitor Resistance in Cancer Immunotherapy.Pharmaceutics · 2023Review
- Modulation of Radiation Doses and Chimeric Antigen Receptor T Cells: A Promising New Weapon in Solid Tumors-A Narrative Review.Journal of personalized medicine · 2023Review
- Radiotherapy plus CAR-T cell therapy to date: A note for cautions optimism?Frontiers in immunology · 2022Review
- Lactate drives cellular DNA repair capacity: Role of lactate and related short-chain fatty acids in cervical cancer chemoresistance and viral infection.Frontiers in cell and developmental biology · 2022Review
- 3D Breast Tumor Models for Radiobiology Applications.Cancers · 2021Review
- Altered glycolysis results in drug-resistant in clinical tumor therapy.Oncology letters · 2021Review
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- HSP90α Mediates Sorafenib Resistance in Human Hepatocellular Carcinoma by Necroptosis Inhibition under Hypoxia.Cancers · 2021Article
- Effect of Prophylactic Use of Intranasal Oil Formulations in the Hamster Model of COVID-19.Frontiers in pharmacology · 2021Article
- HIF-2α regulates CD44 to promote cancer stem cell activation in triple-negative breast cancerWorld journal of stem cells · 2020Article
- ASK1 Enhances Angiotensin II-Induced Liver FibrosisMediators of inflammation · 2020Article
- Macrophage metabolic reprogramming aggravates aortic dissection through the HIF1α-ADAM17 pathwayEBioMedicine · 2019Article
- Angiotensin II Increases Endoplasmic Reticulum Stress in Adipose Tissue and Adipocytes.Scientific reports · 2019Article
- EXPRESSION OF THE RENIN-ANGIOTENSIN SYSTEM COMPONENTS IN ONCOLOGIC DISEASES.Acta clinica Croatica · 2019Review
- Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications.Oxidative medicine and cellular longevity · 2019Review
- Renin-angiotensin inhibitors reprogram tumor immune microenvironment: A comprehensive view of the influences on anti-tumor immunity.Oncotarget · 2018Review
- Local angiotensin II contributes to tumor resistance to checkpoint immunotherapy.Journal for immunotherapy of cancer · 2018Article
- Role of metabolism in cancer cell radioresistance and radiosensitization methods.Journal of experimental & clinical cancer research : CR · 2018Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism. We further demonstrate in nasopharyngeal carcinoma CNE2 and 5-8F cells that this chymase-dependent effect is mediated by increased levels of lactate, a by-product of glycolytic metabolism. Finally, we show that the enhanced angiotensin II plays an important role in the intracellular accumulation of HIF-1α of hypoxic nasopharyngeal carcinoma cells and mediates the radiation-resistant phenotype of these nasopharyngeal carcinoma cells. Thus, our findings reveal the critical role of hypoxia in producing local angiotensin II by a lactate-chymase-dependent mechanism and highlight the importance of local angiotensin II in regulating radioresistance of hypoxic tumor cells.
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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.