ArticlePloS one2012
Time-dependent stabilization of hypoxia inducible factor-1α by different intracellular sources of reactive oxygen species.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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.
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
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- The Role of NRF2 in Cerebrovascular Protection: Implications for Vascular Cognitive Impairment and Dementia (VCID).International journal of molecular sciences · 2024Review
- Monoamine oxidase mediated oxidative stress: a potential molecular and biochemical crux in the pathogenesis of obesity.Molecular biology reports · 2023Review
- Mitochondrial reactive oxygen species modify extracellular vesicles secretion rate.FASEB bioAdvances · 2023Article
- The role of hypoxia-inducible factor 1 alpha (HIF-1α) modulation in heavy metal toxicity.Archives of toxicology · 2023Review
- Tumor microenvironment interactions with cancer stem cells in pancreatic ductal adenocarcinoma.Advances in cancer research · 2023Review
- Emerging role of circRNAs in cancer under hypoxia.Oncology letters · 2022Review
- Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Tumour Microenvironment Stress Promotes the Development of Drug Resistance.Antioxidants (Basel, Switzerland) · 2021Review
- Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- β3-Adrenoreceptors as ROS Balancer in Hematopoietic Stem Cell Transplantation.International journal of molecular sciences · 2021Review
- Targeting hypoxic tumor microenvironment in pancreatic cancer.Journal of hematology & oncology · 2021Review
- ROS as Regulators of Cellular Processes in Melanoma.Oxidative medicine and cellular longevity · 2021Review
- Understanding the Oxygen-Sensing Pathway and Its Therapeutic Implications in Diseases.The American journal of pathology · 2020Review
- Redox Homeostasis and Metabolism in Cancer: A Complex Mechanism and Potential Targeted Therapeutics.International journal of molecular sciences · 2020Review
- Metabolic Modulation of Macrophage Function Post Myocardial Infarction.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intratumoral hypoxia is a major obstacle in the development of effective cancer chemotherapy, decreasing the efficacy of anti-neoplastic drugs in several solid tumours. The hypoxic environment, through its master regulator hypoxia inducible factor-1 (HIF-1), is able to maintain an anti-apoptotic potential through activation of critical genes associated with drug resistance. Besides affecting metabolism and motility of tumour cells, hypoxia also paradoxically increases production of reactive oxygen species (ROS), which contribute to stabilize HIF-1 through a redox-mediated inhibition of its proteolysis. Here we reported that 1% O(2) hypoxia increases the resistance of human metastatic melanoma cells to conventional chemotherapy with etoposide, and that the increase in chemoresistance strongly depends on ROS delivery due to hypoxia. We reported a biphasic redox-dependent role of HIF-1, involving mitochondrial complex III and NADPH oxidase as oxidants sources, synergising in enhancing survival to chemotherapy. The feed-forward loop engaged by hypoxia involves first an HIF-1-dependent vascular endothelial growth factor-A (VEGF-A) autocrine production and, in the later phase, activation of NADPH oxidase from VEGF/VEGFR2 interaction, finally leading to a further redox-dependent long lasting stabilization of HIF-1. We therefore identified a redox-dependent circuitry linking hypoxia-driven ROS to VEGF-A secretion and to enhanced melanoma cell survival to etoposide chemotherapy.
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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.