ArticleOncogene2013
Involvement of decreased hypoxia-inducible factor 1 activity and resultant G1-S cell cycle transition in radioresistance of perinecrotic tumor cells.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Laser interstitial thermal therapy (LITT) for brain metastases: a systematic review and pooled analysis of Efficacy/Safety and the role of combination treatments.Journal of neuro-oncology · 2026Pooled it
- Quantitative dissection of radioresistance in cancer cells: Oxygen depletion-induced biological versus chemical mechanisms and baseline mechanisms governed by HIF-1β-NRF2/TXNRD1.Neoplasia (New York, N.Y.) · 2026Article
- Hypoxia- and Postirradiation reoxygenation-induced HMHA1/ARHGAP45 expression contributes to cancer cell invasion in a HIF-dependent manner.British journal of cancer · 2024Article
- Radiotherapy plus CAR-T cell therapy to date: A note for cautions optimism?Frontiers in immunology · 2022Review
- SPINK1 as a plasma marker for tumor hypoxia and a therapeutic target for radiosensitization.JCI insight · 2021Article
- Space Radiation Biology for "Living in Space".BioMed research international · 2020Review
- Transportable system enabling multiple irradiation studies under simultaneous hypoxia in vitro.Radiation oncology (London, England) · 2018Article
- Influence of c-Src on hypoxic resistance to paclitaxel in human ovarian cancer cells and reversal of FV-429.Cell death & disease · 2018Article
- Hypoxia inducible factor-1α regulates autophagy via the p27-E2F1 signaling pathway.Molecular medicine reports · 2017Article
- Inhibition of Notch and HIF enhances the antitumor effect of radiation in Notch expressing lung cancer.International journal of clinical oncology · 2017Article
- Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells.PloS one · 2017Article
- EBV-LMP1 targeted DNAzyme enhances radiosensitivity by inhibiting tumor angiogenesis via the JNKs/HIF-1 pathway in nasopharyngeal carcinoma.Oncotarget · 2015Article
- UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α.Nature communications · 2015Article
- Baicalin inhibits hypoxia-induced pulmonary artery smooth muscle cell proliferation via the AKT/HIF-1α/p27-associated pathway.International journal of molecular sciences · 2014Article
- HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs.Scientific reports · 2014Article
- Targeting hypoxia in the leukemia microenvironment.International journal of hematologic oncology · 2013Article
- Lin28 mediates radiation resistance of breast cancer cells via regulation of caspase, H2A.X and Let-7 signaling.PloS one · 2013Article
- Microenvironments and cellular characteristics in the micro tumor cords of malignant solid tumors.International journal of molecular sciences · 2012Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer patients often suffer from local tumor recurrence after radiation therapy. Some intracellular and extracellular factors, such as activity of hypoxia-inducible factor 1 (HIF-1), cell cycle status and oxygen availability, have been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. But when, where, and how these factors affect one another and induce cellular radioresistance is largely unknown. Here, we analyzed mechanistic and spatio-temporal relationships among them in highly heterogeneous tumor microenvironments. Experiments in vitro demonstrated that a decrease in the glucose concentration reduced the transcriptional activity of HIF-1 and expression of a downstream gene for the cell cycle regulator p27(Kip1) even under hypoxic conditions. Then, the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased, significantly. Immunohistochemical analyses showed that cancer cells in perinecrotic hypoxic regions, which should be under low-glucose conditions, expressed little HIF-1α, and therefore, were mainly in S phase and less damaged by radiation treatment. Continuous administration of glucagon, which increases the blood glucose concentration and so improves glucose availability in perinecrotic hypoxic regions, induced HIF-1α expression and increased radiation-induced DNA damage. Taken all together, these results indicate that cancer cells in perinecrotic regions, which would be under low-glucose and hypoxic conditions, obtain radioresistance by decreasing the level of both HIF-1 activity and p27(Kip1) expression, and adjusting their cell cycle to the radioresistant S phase.
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