Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways
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Published:2022-10-31
Issue:21
Volume:23
Page:13240
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Lee Eun Hye, Chung Jae-WookORCID, Sung Eunji, Yoon Bo Hyun, Jeon Minji, Park SongORCID, Chun So Young, Lee Jun Nyung, Kim Bum SooORCID, Kim Hyun TaeORCID, Kim Tae Hwan, Choi Seock Hwan, Yoo Eun Sang, Kwon Tae Gyun, Kang Ho Won, Kim Wun-JaeORCID, Yun Seok JoongORCID, Lee SangkyuORCID, Ha Yun-SokORCID
Abstract
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.
Funder
National Research Foundation of Korea Korean government Business for Cooperative R&D between Industry, Academy, and Research Institute Korea Small and Medium Business Administration
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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