ArticleCellular oncology (Dordrecht, Netherlands)2021
Hypoxia-induced ROS promotes mitochondrial fission and cisplatin chemosensitivity via HIF-1α/Mff regulation in head and neck squamous cell carcinoma.
Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Sinapic Acid Reduces Hypoxia-Induced Cell Damage in Hep-2 Cells by Regulating TRPM2 Channel Activation.Journal of biochemical and molecular toxicology · 2026Article
- Integrated transcriptomics identifies HIF1A and GSTP1 as biomarkers for cutaneous squamous cell carcinoma.Translational cancer research · 2026Article
- Imbalances of mitochondrial dynamics in solid tumors.Oncogenesis · 2026Review
- Mitochondrial fission factor drives an actionable metabolic vulnerability in multiple myeloma.Haematologica · 2025Article
- Effects of hypoxia stress on the milk synthesis in bovine mammary epithelial cells.Journal of animal science and biotechnology · 2025Article
- Mitochondrial dynamics in cisplatin resistance: molecular mechanisms and therapeutic targeting.Frontiers in oncology · 2025Review
- DuringAutophagy reports · 2025Article
- Mitochondria-associated non-coding RNAs and their impact on drug resistance.Frontiers in pharmacology · 2025Review
- CPLX2 is a novel tumor suppressor and improves the prognosis in glioma.Journal of neuro-oncology · 2024Article
- ROS are required for the germinative cell proliferation and metacestode larval growth ofFrontiers in microbiology · 2024Article
- Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increased Mitochondrial Fission In Vitro and Atherosclerosis in High-Fat-Diet-Fed ApoEInternational journal of molecular sciences · 2023Article
- Sirtuin4 alleviates severe acute pancreatitis by regulating HIF-1α/HO-1 mediated ferroptosis.Cell death & disease · 2023Article
- HIF-1 signaling: an emerging mechanism for mitochondrial dynamics.Journal of physiology and biochemistry · 2023Review
- The PRAK-NRF2 axis promotes the differentiation of Th17 cells by mediating the redox homeostasis and glycolysis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Hypoxia-induced oxidative stress promotes therapy resistance via upregulation of heme oxygenase-1 in multiple myeloma.Cancer medicine · 2023Article
- Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma.Journal of Zhejiang University. Science. B · 2023Article
- Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets.Frontiers in physiology · 2023Review
- Unique metabolism and protein expression signature in human decidual NK cells.Frontiers in immunology · 2023Article
- The role of Mitochondrial Fission Proteins in Mitochondrial Dynamics in Kidney Disease.International journal of molecular sciences · 2022Review
- Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
purposeChemotherapy based on cisplatin (CDDP) has been established as the treatment of choice for head and neck squamous cell carcinoma (HNSCC). Malignant tumors respond to microenvironmental alterations through a dynamic balance between mitochondrial fission and fusion. HNSCCs are known to exhibit hypoxic conditions, yet the respective effects and underlying mechanisms of hypoxia on chemosensitivity and mitochondrial dynamics remain to be resolved.
methodsThe effect of hypoxia on the chemosensitivity of HNCC cells was determined by flow cytometry. Mitochondrial fission factor (Mff) expression was assessed by RT-PCR and Western blotting in hypoxic HNSCC cells, and further verified in primary CDDP-sensitive and CDDP-resistant HSNCC samples. The biological function of Mff was evaluated by loss of function and gain of function analyses, both in vitro and in vivo.
resultsWe found that hypoxia promoted mitochondrial fission and CDDP sensitivity in HNSCC cells. Importantly, Mff was found to be correlated with chemosensitivity in primary clinical samples under hypoxic conditions. Hypoxia-inducible factor 1α (HIF-1α) was found to markedly increase Mff transcription and to directly bind to Mff. Hypoxia enhanced the release of reactive oxygen species (ROS) and upregulated the expression of Mff via HIF-1α in HNSCC cells. ROS depletion in HNSCC cells attenuated HIF-1α expression, Mff expression and mitochondrial fission. Moreover, Mff knockdown led to suppression of hypoxia-induced mitochondrial fission and to decreased CDDP chemosensitivity in vivo and in vitro.
conclusionsOur findings indicate that hypoxia-induced release of ROS can promote mitochondrial fission and CDDP chemosensitivity via HIF1α/Mff regulation in HNSCC cells, indicating that Mff may serve as a biomarker to predict neoadjuvant chemosensitivity in HNSCC patients and as a target for overcoming chemoresistance.
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