ArticleProceedings of the National Academy of Sciences of the United States of America2014
Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia-cell cycle dual reporter.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 57 citations in OpenAlex.
- Mitochondrial Metabolism and Dynamics in Cancer Cells.Cancer treatment and research · 2026Review
- Examining structure-activity relationships of ManNAc analogs used in the metabolic glycoengineering of human neural stem cells.Biomaterials advances · 2025Article
- A novel lineage-tracing tool reveals that hypoxic tumor cells drive tumor relapse after radiotherapy.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- Limited oxygen in standard cell culture alters metabolism and function of differentiated cells.The EMBO journal · 2024Article
- Review
- Mapping the Fate of Hypoxic Cells Using an Irreversible Fluorescent Switch.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Ex vivo expansion of circulating tumour cells (CTCs).Scientific reports · 2023Article
- Lactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α activity promoting proliferation of hypoxic cells.Cell systems · 2022Article
- Review
- Dcf1 induces glioblastoma cells apoptosis by blocking autophagy.Cancer medicine · 2022Article
- Mitochondrial Redox Metabolism: The Epicenter of Metabolism during Cancer Progression.Antioxidants (Basel, Switzerland) · 2021Review
- Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Review
- Inhibition of glutaminolysis in combination with other therapies to improve cancer treatment.Current opinion in chemical biology · 2021Review
- Glucose Metabolism in Cancer: The Warburg Effect and Beyond.Advances in experimental medicine and biology · 2021Article
- Different Tumor Microenvironments Lead to Different Metabolic Phenotypes.Advances in experimental medicine and biology · 2021Article
- The Intratumoral Heterogeneity of Cancer Metabolism.Advances in experimental medicine and biology · 2021Article
- Mitochondrial Metabolism as a Target for Cancer Therapy.Cell metabolism · 2020Review
- Genetically Encoded Tools for Research of Cell Signaling and Metabolism under Brain Hypoxia.Antioxidants (Basel, Switzerland) · 2020Review
- Cyclin-Dependent Kinase and Antioxidant Gene Expression in Cancers with Poor Therapeutic Response.Pharmaceuticals (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Although aerobic glycolysis provides an advantage in the hypoxic tumor microenvironment, some cancer cells can also respire via oxidative phosphorylation. These respiring ("non-Warburg") cells were previously thought not to play a key role in tumorigenesis and thus fell from favor in the literature. We sought to determine whether subpopulations of hypoxic cancer cells have different metabolic phenotypes and gene-expression profiles that could influence tumorigenicity and therapeutic response, and we therefore developed a dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia-inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a model, we identified four distinct hypoxic cell populations by flow cytometry. The non-HIF/noncycling cell population expressed a unique set of genes involved in mitochondrial function. Relative to the other subpopulations, these hypoxic "non-Warburg" cells had highest oxygen consumption rates and mitochondrial capacity consistent with increased mitochondrial respiration. We found that these respiring cells were unexpectedly tumorigenic, suggesting that continued respiration under limiting oxygen conditions may be required for tumorigenicity.
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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.