Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 21, Pages -Publisher
MDPI
DOI: 10.3390/ijms232113240
Keywords
bladder cancer; metastasis; invasion; muscle-invasive bladder cancer (MIBC); pyruvate dehydrogenase kinase 4 (PDK4)
Funding
- National Research Foundation of Korea (NRF) - Korean government (MSIT) [2019R1A2C1004046, 2020R1A2B5B03002344, 2020R1I1A3071568, 2021R1G1A1092985, 2022R1I1A3069482]
- Industry, Academy, and Research Institute - Korea Small and Medium Business Administration [S3106172]
- Korea Technology & Information Promotion Agency for SMEs (TIPA) [S3106172] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2022R1I1A3069482, 2021R1G1A1092985] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This study evaluated the role of PDK4 in bladder cancer and its related protein changes. It was found that elevated expression of PDK4 was observed in high-grade bladder cancers. Knockdown of PDK4 in bladder cancer cells resulted in reduced cell migration and invasion. Additionally, a PDK4 knockdown xenograft model showed reduced bladder cancer growth. These findings suggest that PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.
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.
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