ArticleOncotarget2017
Clinically relevant HIF-1α-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Prognostic value of CAIX expression in oral squamous cell carcinoma: a systematic review and meta-analysis.Journal of enzyme inhibition and medicinal chemistry · 2020Pooled it
- A dual role for miR-210-3p in hypoxia-driven signaling and mitotic regulation in cancer.Molecular biomedicine · 2026Article
- Polar cell membrane nanotubes containing microtubules and acidic vesicles render Drosophila eggs fertile.PLoS biology · 2025Article
- The Single Nucleotide Substitution T → A rs2072580 Damages the CREB1 Binding Site in the BidirectionalGenes · 2025Article
- Deciphering the role of circular RNAs in cancer progression under hypoxic conditions.Medical oncology (Northwood, London, England) · 2025Review
- Tumor hypoxia and role of hypoxia-inducible factor in oral cancer.World journal of surgical oncology · 2024Review
- Metabolic heterogeneity in early-stage lung adenocarcinoma revealed by RNA-seq and scRNA-seq.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- HIF: a master regulator of nutrient availability and metabolic cross-talk in the tumor microenvironment.The EMBO journal · 2023Review
- Emerging role of miRNAs in the regulation of ferroptosis.Frontiers in molecular biosciences · 2023Review
- SLC-0111, an inhibitor of carbonic anhydrase IX, attenuates hepatoblastoma cell viability and migration.Frontiers in oncology · 2023Article
- Review
- Extracellular vesicles miR-210 as a potential biomarker for diagnosis and survival prediction of oral squamous cell carcinoma patients.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2022Article
- Review
- Carbonic Anhydrase III Attenuates Hypoxia-Induced Apoptosis and Activates PI3K/Akt/mTOR Pathway in H9c2 Cardiomyocyte Cell Line.Cardiovascular toxicology · 2021Article
- TINCR inhibits the proliferation and invasion of laryngeal squamous cell carcinoma by regulating miR-210/BTG2.BMC cancer · 2021Article
- Altered glycolysis results in drug-resistant in clinical tumor therapy.Oncology letters · 2021Review
- Peering into tunneling nanotubes-The path forward.The EMBO journal · 2021Review
- CD90 affects the biological behavior and energy metabolism level of gastric cancer cells by targeting the PI3K/AKT/HIF-1α signaling pathway.Oncology letters · 2021Article
- Intrinsically disordered features of carbonic anhydrase IX proteoglycan-like domain.Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs. Cell-based analysis revealed that HIF-1α-driven metabolic program includes over-expression of glycolytic enzymes and the microRNA miR-210 coupled to down-regulation of its target, the iron-sulfur cluster assembly protein, ISCU. pH-regulator program entailed over-expression of CAIX, but not MCT1 or MCT4. Accordingly, significant overlapping exists between over-expression of HIF-1α and CAIX, but not HIF-1α and MCT1 or MCT4, in tumor cells. Increased miR-210 and concomitant decreased ISCU RNA levels were found in ~40% of tumors and this was significantly associated with HIF-1α and CAIX, but not MCT1 or MCT4, over-expression. HIF-1α and/or CAIX over-expression was associated with high recurrence rate and low overall survival of surgically treated patients. By contrast, clinically significant correlations were not found in tumors with MCT1 or MCT4 over-expression. This is the first study that provides in vivo evidences of coordinated activation of HIF-1α, CAIX, miR-210 and ISCU in carcinoma and association with poor prognosis, a finding with important implications for the development of metabolic-targeting therapies against hypoxia.
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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.