Background: Lung cancer is one of the most leading causes of cancer-related deaths in adults worldwide.
Non-Small Cell Lung Cancer (NSCLC), which comprises 80 to 85% of all lung cancers, is the most lethal subtype of
lung cancer with a 5-year survival of less than 13%. In this study, we identified a poorly-studied kinase PDK4 as the
most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma.
Methods: In vitro cell viability assay and in vivo tumor xenograft assay were used in the detection of cell proliferation.
RNA isolation, quantitative Real-Time PCR, Western blot analysis, immunohistochemistry were used to investigate
the expression of RNA and protein. Lentivirus infection was used to regulate gene expression. Luciferase assays
were used to monitor EPAS1 promoter activity.
Results: In vivo PDK4 expression was elevated in a Cisplatin-resistant population of lung adenocarcinoma cells,
PDK4-dependent Cisplatin-resistance promotes tumor growth of lung adenocarcinoma in vivo and in vitro, clinically
PDK4 expression was associated with poor prognosis in lung adenocarcinoma patients, mechanically PDK4 promoted
cell growth and Cisplatin-resistance of lung adenocarcinoma via transcriptional regulation of endothelial PAS
domain-containing protein 1 (EPAS1).
Conclusion: PDK4 is the most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma and
PDK4-dependent Cisplatin-resistance promotes tumor growth of lung adenocarcinoma mainly through transcriptional
regulation of EPAS1. Enriched PDK4 expression was correlated with the poor prognosis of lung cancer patients,
indicating that PDK4 could be a potential therapeutic target for Cisplatin-resistant lung adenocarcinoma.