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丙酮酸脱氢酶激酶 4 抑制通过 ERK、SRC 和 JNK 通路在膀胱癌中的抗转移作用。

Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways.

机构信息

Joint Institute of Regenerative Medicine, Kyungpook National University, Daegu 41566, Korea.

Department of Urology, School of Medicine, Kyungpook National University, Daegu 41405, Korea.

出版信息

Int J Mol Sci. 2022 Oct 31;23(21):13240. doi: 10.3390/ijms232113240.

DOI:10.3390/ijms232113240
PMID:36362028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9658024/
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.

摘要

膀胱癌是一种常见的全球癌症，转移率高，死亡率高。因此，有必要寻找新的生物标志物，以便于诊断。丙酮酸脱氢酶激酶 4（PDK4）属于 PDK 家族，在生物体内葡萄糖利用中发挥重要作用。在本研究中，我们评估了 PDK4 在膀胱癌中的作用及其相关蛋白的变化。首先，我们观察到高级别膀胱癌中 PDK4 表达升高。为了筛选膀胱癌中与 PDK4 相关的蛋白变化，我们使用 PDK4 敲低细胞进行了比较蛋白质组学分析。在膀胱癌细胞系中，PDK4 沉默导致细胞迁移和侵袭率降低。此外，PDK4 敲低的异种移植模型显示在裸鼠中膀胱癌生长减少。基于我们的结果，PDK4 通过改变 ERK、SRC 和 JNK，在膀胱癌细胞的转移和生长中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/c437ae7cf889/ijms-23-13240-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/95683f87ec42/ijms-23-13240-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/20fea24f2633/ijms-23-13240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/e77206e2133b/ijms-23-13240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/e36bf56be3d3/ijms-23-13240-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/c437ae7cf889/ijms-23-13240-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/95683f87ec42/ijms-23-13240-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/c6da02172eb5/ijms-23-13240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/20fea24f2633/ijms-23-13240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/e77206e2133b/ijms-23-13240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/e36bf56be3d3/ijms-23-13240-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7270/9658024/c437ae7cf889/ijms-23-13240-g006.jpg

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