ArticleCancer chemotherapy and pharmacology2021
PDK4 promotes tumorigenesis and cisplatin resistance in lung adenocarcinoma via transcriptional regulation of EPAS1.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
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- PDK4 expression and tumor aggressiveness in prostate cancer.Investigative and clinical urology · 2025Article
- Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer.Current molecular medicine · 2025Review
- Long-term high fat diet aggravates the risk of lung fibrosis and lung cancer: transcriptomic analysis in the lung tissues of obese mice.Translational lung cancer research · 2024Article
- Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.Cancer medicine · 2024Article
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- A novel anoikis-related prognostic signature associated with prognosis and immune infiltration landscape in clear cell renal cell carcinoma.Frontiers in genetics · 2022Article
- Identification and validation of an anoikis-associated gene signature to predict clinical character, stemness, IDH mutation, and immune filtration in glioblastoma.Frontiers in immunology · 2022Article
- Pyruvate dehydrogenase kinase 4-mediated metabolic reprogramming is involved in rituximab resistance in diffuse large B-cell lymphoma by affecting the expression of MS4A1/CD20.Cancer science · 2021Article
- Identification of Immune-Related Risk Characteristics and Prognostic Value of Immunophenotyping in TNBC.Frontiers in genetics · 2021Article
- Autophagy and Glycometabolic Reprograming in the Malignant Progression of Lung Cancer: A Review.Technology in cancer research & treatmentReview
- Integrated Analysis Identifies an Anoikis-Related Gene Signature for Predicting Prognosis in Patients With Triple-Negative Breast Cancer.IET systems biologyArticle
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of cisplatin for the treatment of non-small cell lung cancer has long been constrained by the rapid acquisition of tumor cell chemoresistance. In the present study, we sought to better elucidate the molecular mechanisms underlying this resistance phenotype. To that end, we assessed gene expression patterns in cisplatin-resistant lung adenocarcinoma cells, revealing pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4) to be the most up-regulated kinase in resistant cells. We further found PDK4 upregulation to be directly linked with the acquisition of chemoresistance, driving enhanced tumor cell growth in vitro and in vivo. In clinical samples, we also found that PDK4 upregulation was detectable in patients with lung adenocarcinoma and that it was correlated with a poorer prognosis for these patients. From a mechanistic perspective, we further determined that PDK4 was able to promote lung adenocarcinoma cell growth and cisplatin resistance at least in part via regulating endothelial PAS domain-containing protein 1 (EPAS1) expression, thus highlighting PDK4 as a potentially viable therapeutic target in efforts to treat lung adenocarcinoma patients that have become resistant to cisplatin.
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