ArticleGenes & diseases2024
PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α.
Article in Genes & diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- PDK1 elevation was induced by epigenetic modifications of KDM3A and METTL16 to mediate TKI resistance and cancer development.Genes & diseases · 2026Article
- Targeting the Warburg Effect in Anaplastic Thyroid Carcinoma: Metabolic Vulnerabilities and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Intermittent fasting synergizes with GCN5 inhibition to suppress RBM5-AS1/GCN5/PGC-1α-driven Warburg metabolism in ovarian cancer.Functional & integrative genomics · 2026Article
- LncPVT1 modulates decidualization and links to recurrent spontaneous abortions via glucose and lipid metabolic regulation.Scientific reports · 2026Article
- PI3K/Akt/mTOR signaling pathway mediates energy metabolic reprogramming and regulates mitochondrial homeostasis in host cells exposed toMicrobiology spectrum · 2026Article
- Mutant p53 Regulates Pyruvate Dehydrogenase Kinase 1 (PDK1) to Promote Proliferation and Migration in Breast Cancer.Cancer science · 2026Article
- Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- PDK1-dependent metabolic reprogramming regulates stemness and tumorigenicity of osteosarcoma stem cells through ATF3.Cell death & disease · 2025Article
- Review
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- IGLL5 has potential to be a prognostic biomarker and its correlation with immune infiltrates in breast cancer.American journal of clinical and experimental immunology · 2025Article
- Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak.Frontiers in veterinary science · 2025Article
- Addressing the mean-variance relationship in spatially resolved transcriptomics data withbioRxiv : the preprint server for biology · 2024Article
- Study on the Regulatory Mechanism of the PDK1-Mediated TGF-β/Smad Signaling Pathway in Hypoxia-Induced Yak Lungs.Animals : an open access journal from MDPI · 2024Article
- Hypoxia-induced epigenetic regulation of breast cancer progression and the tumour microenvironment.Frontiers in cell and developmental biology · 2024Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate dehydrogenase kinase 1 (PDK1) phosphorylates the pyruvate dehydrogenase complex, which inhibits its activity. Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis, which plays an important role in tumor progression. This study aims to elucidate how PDK1 promotes breast cancer progression. We found that PDK1 was highly expressed in breast cancer tissues, and PDK1 knockdown reduced the proliferation, migration, and tumorigenicity of breast cancer cells and inhibited the HIF-1α (hypoxia-inducible factor 1α) pathway. Further investigation showed that PDK1 promoted the protein stability of HIF-1α by reducing the level of ubiquitination of HIF-1α. The HIF-1α protein levels were dependent on PDK1 kinase activity. Furthermore, HIF-1α phosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells. The phosphorylation of HIF-1α at Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1α with von Hippel-Lindau and prolyl hydroxylase domain. We also found that PDK1 enhanced HIF-1α transcriptional activity. In summary, PDK1 enhances HIF-1α protein stability by phosphorylating HIF-1α at Ser451 and promotes HIF-1α transcriptional activity by enhancing the binding of HIF-1α to P300. PDK1 and HIF-1α form a positive feedback loop to promote breast cancer progression.
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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.