Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways.
Eun Hye LeeJae Wook ChungEunji SungBo Hyun YoonMinji JeonSong ParkSo Young ChunJun Nyung LeeBum Soo KimHyun Tae KimTae Hwan KimSeock Hwan ChoiEun Sang YooTae Gyun KwonHo Won KangWun Jae KimSeok-Joong YunSang-Kyu LeeYun Sok HaPublished in: International journal of molecular sciences (2022)
Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.
Keyphrases
- signaling pathway
- induced apoptosis
- high grade
- tyrosine kinase
- spinal cord injury
- squamous cell carcinoma
- cell death
- poor prognosis
- small cell lung cancer
- stem cells
- type diabetes
- single cell
- papillary thyroid
- cardiovascular events
- metabolic syndrome
- high throughput
- low grade
- cell cycle arrest
- muscle invasive bladder cancer
- adipose tissue
- endoplasmic reticulum stress
- protein kinase