Lee Eun Hye, Ha Yun-Sok, Yoon Bo Hyun, Jeon Minji, Park Dong Jin, Kim Jiyeon, Kang Jun-Koo, Chung Jae-Wook, Kim Bum Soo, Choi Seock Hwan, Kim Hyun Tae, Kim Tae-Hwan, Yoo Eun Sang, Kwon Tae Gyun
Joint Institute of Regenerative Medicine, Kyungpook National University, Daegu, Korea.
Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea.
Investig Clin Urol. 2025 May;66(3):227-235. doi: 10.4111/icu.20240434.
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.
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.
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.
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.
前列腺癌是全球男性中第二常见的癌症，是癌症相关死亡率的一个重要原因。转移，即癌细胞从原发部位扩散到远处器官，仍然是前列腺癌治疗中的一个主要挑战。丙酮酸脱氢酶激酶4（PDK4）参与有氧糖酵解的调节，在各种癌症中成为一个潜在的因素。然而，其在前列腺癌中的作用仍不清楚。本研究旨在分析PDK4在前列腺癌细胞和人体样本中的表达，并探讨该基因的临床意义。
检测细胞系和人体组织样本中PDK4的表达。使用基质胶包被的侵袭小室分析迁移能力。人体样本取自庆北国立大学칠곡医院。
与正常前列腺细胞相比，前列腺癌细胞系中PDK4的表达升高，在DU145和LnCap细胞系中水平尤其高。这些细胞系中PDK4的敲低抑制了它们的侵袭能力，表明PDK4在前列腺癌转移中具有潜在作用。此外，我们的结果显示PDK4抑制后上皮-间质转化标志物和下游信号分子发生改变，提示其参与侵袭相关途径的调节。此外，与正常前列腺组织相比，前列腺癌组织中PDK4的表达增加，尤其是在去势抵抗性前列腺癌中，前列腺特异性抗原（PSA）和PDK4的表达呈显著正相关。
前列腺癌中PDK4的表达与肿瘤侵袭和去势状态相关。需要进一步验证以证明其作为治疗靶点的有效性。
