ArticleFrontiers in cell and developmental biology2021
Pyruvate Dehydrogenase Contributes to Drug Resistance of Lung Cancer Cells Through Epithelial Mesenchymal Transition.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 18 citations in OpenAlex.
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- PDHA1 Hyperactivation Orchestrates Metabolic Reprogramming Promoting Endothelial Senescence.Research (Washington, D.C.) · 2026Article
- Mitochondrial Dysfunction in Apoptosis-Resistant Acute Myeloid Leukemia Cells During a Sterile Inflammatory Response.Biomolecules · 2025Article
- Cholangiocarcinoma PDHA1 succinylation suppresses macrophage antigen presentation via alpha-ketoglutaric acid accumulation.Nature communications · 2025Article
- Identification and validation of mitochondrial and programmed cell death-related prognostic markers in pediatric acute myeloid leukemia.Frontiers in immunology · 2025Article
- Joint analysis of mutational and transcriptional landscapes in human cancer reveals key perturbations during cancer evolution.Genome biology · 2024Article
- Unveiling the mechanisms and challenges of cancer drug resistance.Cell communication and signaling : CCS · 2024Review
- Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine.Journal of advanced research · 2024Review
- Dual LSD1 and HDAC6 Inhibition Induces Doxorubicin Sensitivity in Acute Myeloid Leukemia Cells.Cancers · 2022Article
- Intrinsic adaptations in OXPHOS power output and reduced tumorigenicity characterize doxorubicin resistant ovarian cancer cells.Biochimica et biophysica acta. Bioenergetics · 2022Article
- Label-Free Quantitative Proteomics Analysis of Adriamycin Selected Multidrug Resistant Human Lung Cancer Cells.Biomolecules · 2022Article
- Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, there has been a growing interest on the role of mitochondria in metastatic cascade. Several reports have shown the preferential utilization of glycolytic pathway instead of mitochondrial respiration for energy production and the pyruvate dehydrogenase (PDH) has been considered to be a contributor to this switch in some cancers. Since epithelial mesenchymal transition (EMT) is proposed to be one of the significant mediators of metastasis, the molecular connections between cancer cell metabolism and EMT may reveal underlying mechanisms and improve our understanding on metastasis. In order to explore a potential role for PDH inhibition on EMT and associated drug resistance, we took both pharmacological and genetic approaches, and selectively inhibited or knocked down PDHA1 by using Cpi613 and shPDHA1, respectively. We found that both approaches triggered morphological changes and characteristics of EMT (increase in mesenchymal markers). This change was accompanied by enhanced wound healing and an increase in migration. Interestingly, cells were more resistant to many of the clinically used chemotherapeutics following PDH inhibition or PDHA1 knockdown. Furthermore, the TGF
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