ArticleAmerican journal of cancer research2018
Targeting PDK4 inhibits breast cancer metabolism.
Article in American journal of cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- Lapatinib-Loaded Glucose-Functionalized Silver Nanoparticles Enhance Efficacy in HER2-Positive Breast Cancer Cells and Modulate Survival-Associated Genes.Pharmaceutical research · 2026Article
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- Multi-dimensional analysis reveals the potential of PDK4 as a tumor biomarker and target for immunotherapy.Discover oncology · 2026Article
- Reducing PDK4 level constitutes a pivotal mechanism for glucocorticoids to impede osteoblastic differentiation through the enhancement of ferroptosis in mesenchymal stem cells.Stem cell research & therapy · 2025Article
- Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer.Nature aging · 2025Article
- MicroRNAs and their role in breast cancer metabolism (Review).International journal of oncology · 2025Review
- Inhibition of Pyruvate Dehydrogenase Kinase 4 Protects Cardiomyocytes from lipopolysaccharide-Induced Mitochondrial Damage by Reducing Lactate Accumulation.Inflammation · 2024Article
- Abrogating PDK4 activates autophagy-dependent ferroptosis in breast cancer via ASK1/JNK pathway.Journal of cancer research and clinical oncology · 2024Article
- Glut-3 Gene Knockdown as a Potential Strategy to Overcome Glioblastoma Radioresistance.International journal of molecular sciences · 2024Article
- Mitochondrial-related genes as prognostic and metastatic markers in breast cancer: insights from comprehensive analysis and clinical models.Frontiers in immunology · 2024Article
- Comprehensive single cell aging atlas of mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer.bioRxiv : the preprint server for biology · 2023Article
- Robust Identification of Differential Gene Expression Patterns from Multiple Transcriptomics Datasets for Early Diagnosis, Prognosis, and Therapies for Breast Cancer.Medicina (Kaunas, Lithuania) · 2023Article
- ZNRF2 as an oncogene is transcriptionally regulated by CREB1 in breast cancer models.Human cell · 2023Article
- Role of microRNAs in glycolysis in gynecological tumors (Review).International journal of oncology · 2023Review
- A Proposed TUSC7/miR-211/Nurr1 ceRNET Might Potentially be Disturbed by a cer-SNP rs2615499 in Breast Cancer.Biochemical genetics · 2022Article
- Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways.International journal of molecular sciences · 2022Article
- Review
- Crosstalk between Hypoxia and Extracellular Matrix in the Tumor Microenvironment in Breast Cancer.Genes · 2022Review
- Cell migration inducing hyaluronidase 1 promotes growth and metastasis of papillary thyroid carcinoma.Bioengineered · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulated metabolism in the form of aerobic glycolysis occurs in many cancers including breast carcinoma. Here, we report PDK4 (pyruvate dehydrogenase kinase 4) as key enzyme implicated in the control of glucose metabolism and mitochondrial respiration is relatively highly expressed in breast cancers, and its expression correlates with poor patient outcomes. Silencing of PDK4 and ectopic expression of miR-211 attenuates PDK4 expression in breast cancer cells. Interestingly, low miR-211 expression is significantly associated with shorter overall survival and reveals an inverse correlation between expression of miR-211 and PDK4. We have found that depletion of PDK4 by miR-211 shows an oxidative phosphorylation-dominant phenotype consisting of the reduction of glucose with increased expression of PDH and key enzymes of the TCA cycle. miR-211 expression causes alteration of mitochondrial membrane potential and induces mitochondrial apoptosis as observed via IPAD assay. Further, by inhibiting PDK4 expression, miR-211 promotes a phenotype shift towards a pro-glycolytic state evidenced by decreased extracellular acidification rate (ECAR); increased oxygen consumption rate (OCR); and increased spare respiratory capacity in breast cancer cell lines. Taken together this data establishes a molecular connection between PDK4 and miR-211 and suggests that targeting miR-211 to inhibit PDK4 could represent a novel therapeutic strategy in breast cancers.
Indexed as
Identifiers
30323966PMC6176187W2993146265What OpenQuestion holds
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.