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

Eun Hye Lee; Jae Wook Chung; Eunji Sung; Bo Hyun Yoon; Minji Jeon; Song Park; So Young Chun; Jun Nyung Lee; Bum Soo Kim; Hyun Tae Kim; Tae Hwan Kim; Seock Hwan Choi; Eun Sang Yoo; Tae Gyun Kwon; Ho Won Kang; Wun Jae Kim; Seok Joong Yun; Sangkyu Lee; Yun Sok Ha

doi:10.3390/ijms232113240

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

Eun Hye Lee, Jae Wook Chung, Eunji Sung, Bo Hyun Yoon, Minji Jeon, Song Park, So Young Chun, Jun Nyung Lee, Bum Soo Kim, Hyun Tae Kim, Tae Hwan Kim, Seock Hwan Choi, Eun Sang Yoo, Tae Gyun Kwon, Ho Won Kang, Wun Jae Kim, Seok Joong Yun, Sangkyu Lee, Yun Sok Ha

Department of Medicine

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English
Article number	13240
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	21
DOIs	https://doi.org/10.3390/ijms232113240
State	Published - Nov 2022

Keywords

bladder cancer
invasion
metastasis
muscle-invasive bladder cancer (MIBC)
pyruvate dehydrogenase kinase 4 (PDK4)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms232113240

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Lee, E. H., Chung, J. W., Sung, E., Yoon, B. H., Jeon, M., Park, S., Chun, S. Y., Lee, J. N., Kim, B. S., Kim, H. T., Kim, T. H., Choi, S. H., Yoo, E. S., Kwon, T. G., Kang, H. W., Kim, W. J., Yun, S. J., Lee, S., & Ha, Y. S. (2022). Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways. International Journal of Molecular Sciences, 23(21), Article 13240. https://doi.org/10.3390/ijms232113240

@article{4dfc90eb1340456cb68495a21c2ada31,

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

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.",

keywords = "bladder cancer, invasion, metastasis, muscle-invasive bladder cancer (MIBC), pyruvate dehydrogenase kinase 4 (PDK4)",

author = "Lee, {Eun Hye} and Chung, {Jae Wook} and Eunji Sung and Yoon, {Bo Hyun} and Minji Jeon and Song Park and Chun, {So Young} and Lee, {Jun Nyung} and Kim, {Bum Soo} and Kim, {Hyun Tae} and Kim, {Tae Hwan} and Choi, {Seock Hwan} and Yoo, {Eun Sang} and Kwon, {Tae Gyun} and Kang, {Ho Won} and Kim, {Wun Jae} and Yun, {Seok Joong} and Sangkyu Lee and Ha, {Yun Sok}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = nov,

doi = "10.3390/ijms232113240",

language = "English",

volume = "23",

journal = "International Journal of Molecular Sciences",

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Lee, EH, Chung, JW, Sung, E, Yoon, BH, Jeon, M, Park, S, Chun, SY, Lee, JN, Kim, BS, Kim, HT, Kim, TH, Choi, SH, Yoo, ES, Kwon, TG, Kang, HW, Kim, WJ, Yun, SJ, Lee, S & Ha, YS 2022, 'Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways', International Journal of Molecular Sciences, vol. 23, no. 21, 13240. https://doi.org/10.3390/ijms232113240

TY - JOUR

T1 - Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways

AU - Lee, Eun Hye

AU - Chung, Jae Wook

AU - Sung, Eunji

AU - Yoon, Bo Hyun

AU - Jeon, Minji

AU - Park, Song

AU - Chun, So Young

AU - Lee, Jun Nyung

AU - Kim, Bum Soo

AU - Kim, Hyun Tae

AU - Kim, Tae Hwan

AU - Choi, Seock Hwan

AU - Yoo, Eun Sang

AU - Kwon, Tae Gyun

AU - Kang, Ho Won

AU - Kim, Wun Jae

AU - Yun, Seok Joong

AU - Lee, Sangkyu

AU - Ha, Yun Sok

PY - 2022/11

Y1 - 2022/11

N2 - 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.

AB - 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.

KW - bladder cancer

KW - invasion

KW - metastasis

KW - muscle-invasive bladder cancer (MIBC)

KW - pyruvate dehydrogenase kinase 4 (PDK4)

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U2 - 10.3390/ijms232113240

DO - 10.3390/ijms232113240

M3 - Article

C2 - 36362028

AN - SCOPUS:85141563229

SN - 1661-6596

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 21

M1 - 13240

ER -

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

Abstract

Keywords

UN SDGs

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