ArticlePloS one2017
Overexpression of pyruvate dehydrogenase kinase 1 in retinoblastoma: A potential therapeutic opportunity for targeting vitreous seeds and hypoxic regions.
Article in PloS one, 2017. 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, 38 citations in OpenAlex.
- Photoreceptor deletion of pyruvate dehydrogenase E1 subunit α1 induces retinal degeneration and reprograms retinal metabolism.Molecular metabolism · 2026Article
- Mutant p53 Regulates Pyruvate Dehydrogenase Kinase 1 (PDK1) to Promote Proliferation and Migration in Breast Cancer.Cancer science · 2026Article
- Unilateral Common Carotid Artery Occlusion in Adult Mice with Streptozotocin Comorbidity Leads to Early Retinal Inflammation.International journal of molecular sciences · 2025Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeting pyruvate dehydrogenase kinase 1 overcomes EGFR C797S mutation-driven osimertinib resistance in non-small cell lung cancer.Experimental & molecular medicine · 2024Article
- Unlocking New Avenues in Breast Cancer Treatment: The Synergy of Kinase Inhibitors and Immunotherapy.Cancers · 2023Review
- A simplified protocol to induce hypoxia in a standard incubator: A focus on retinal cells.Experimental eye research · 2023Article
- AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer.Journal of Zhejiang University. Science. B · 2023Article
- The opportunities and challenges for nutritional intervention in childhood cancers.Frontiers in nutrition · 2023Review
- Early Mechanisms of Chemoresistance in Retinoblastoma.Cancers · 2022Article
- The OncogeneCancers · 2021Article
- Suppression of Pyruvate Dehydrogenase Kinase by Dichloroacetate in Cancer and Skeletal Muscle Cells Is Isoform Specific and Partially Independent of HIF-1α.International journal of molecular sciences · 2021Article
- Allele-Specific MicroRNA-Mediated Regulation of a Glycolysis Gatekeeper PDK1 in Cancer Metabolism.Cancers · 2021Article
- Metabolic Response of Pancreatic Carcinoma Cells under Treatment with Dichloroacetate.Metabolites · 2021Article
- Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer.Molecules (Basel, Switzerland) · 2021Review
- Aurora Kinase B Expression, Its Regulation and Therapeutic Targeting in Human Retinoblastoma.Investigative ophthalmology & visual science · 2021Article
- The oncogenic and prognostic role of PDK1 in the progression and metastasis of ovarian cancer.Journal of Cancer · 2021Article
- Tumor Environment of Retinoblastoma, Intraocular Cancer.Advances in experimental medicine and biology · 2020Article
- Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase.International journal of cancer · 2019Review
- Logical modelling reveals the PDC-PDK interaction as the regulatory switch driving metabolic flexibility at the cellular level.Genes & nutrition · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic reprogramming of tumors, is induced in several tumors including glioblastoma, breast cancer and melanoma. However, the role played by PDK1 is not studied in retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in RB clinical samples, and studied its inhibition as a strategy to decrease cell growth and migration. We show that PDK1 is specifically overexpressed in RB patient samples especially in vitreous seeds and hypoxic regions and cell lines compared to control retina using immunohistochemistry and real-time PCR. Our results further demonstrate that inhibition of PDK1 using small molecule inhibitors dichloroacetic acid (DCA) and dichloroacetophenone (DAP) resulted in reduced cell growth and increased apoptosis. We also confirm that combination treatment of DCA with chemotherapeutic agent carboplatin further enhanced the therapeutic efficacy compared to single drug treatment. In addition, we observed changes in glucose uptake, lactate and reactive oxygen species (ROS) levels as well as decreased cell migration in response to PDK1 inhibition. Additionally, we show that DCA treatment led to inhibition of PI3K/Akt pathway and reduction in PDK1 protein levels. Overall, our data suggest that targeting PDK1 could be a novel therapeutic strategy for RB.
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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.