Investig Clin Urol.  2025 May;66(3):227-235. 10.4111/icu.20240434.

PDK4 expression and tumor aggressiveness in prostate cancer

• Lee EH
• Ha YS
• Yoon BH
• Jeon M
• Park DJ
• Kim J
• Kang JK
• Chung JW
• Kim BS
• Choi SH
• Kim HT
• Kim TH
• Yoo ES
• Kwon TG

• KMID: 2567749
• DOI: http://doi.org/10.4111/icu.20240434

Abstract

Purpose
Prostate cancer ranks as the second most common cancer in men globally, representing a significant cause of cancer-related mortality. Metastasis, the spread of cancer cells from the primary site to distant organs, remains a major challenge in managing prostate cancer. Pyruvate dehydrogenase kinase 4 (PDK4) is implicated in the regulation of aerobic glycolysis, emerging as a potential player in various cancers. However, its role in prostate cancer remains unclear. This study aims to analyze PDK4 expression in prostate cancer cells and human samples, and to explore the gene's clinical significance.
Materials and Methods
PDK4 expression was detected in cell lines and human tissue samples. Migration ability was analyzed using Matrigel-coated invasion chambers. Human samples were obtained from the Kyungpook National University Chilgok Hospital.
Results
PDK4 expression was elevated in prostate cancer cell lines compared to normal prostate cells, with particularly high levels in DU145 and LnCap cell lines. PDK4 knockdown in these cell lines suppressed their invasion ability, indicating a potential role of PDK4 in prostate cancer metastasis. Furthermore, our results revealed alterations in epithelial-mesenchymal transition markers and downstream signaling molecules following PDK4 suppression, suggesting its involvement in the modulation of invasion-related pathways. Furthermore, PDK4 expression was increased in prostate cancer tissues, especially in castration-resistant prostate cancer, compared to normal prostate tissues, with PSA and PDK4 expression showing a significantly positive correlation.
Conclusions
PDK4 expression in prostate cancer is associated with tumor invasion and castration status. Further validation is needed to demonstrate its effectiveness as a therapeutic target.

Keyword

Aggression; Biomarkers; Metastasis; Prostate cancer