Cargando…
Peroxiredoxin I is important for cancer-cell survival in Ras-induced hepatic tumorigenesis
Peroxiredoxin I (Prx I), an antioxidant enzyme, has multiple functions in human cancer. However, the role of Prx I in hepatic tumorigenesis has not been characterized. Here we investigated the relevance and underlying mechanism of Prx I in hepatic tumorigenesis. Prx I increased in tumors of hepatoce...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356538/ https://www.ncbi.nlm.nih.gov/pubmed/27517622 http://dx.doi.org/10.18632/oncotarget.11172 |
_version_ | 1782515855344533504 |
---|---|
author | Han, Bing Shin, Hye-Jun Bak, In Seon Bak, Yesol Jeong, Ye-Lin Kwon, Taeho Park, Young-Ho Sun, Hu-Nan Kim, Cheol-Hee Yu, Dae-Yeul |
author_facet | Han, Bing Shin, Hye-Jun Bak, In Seon Bak, Yesol Jeong, Ye-Lin Kwon, Taeho Park, Young-Ho Sun, Hu-Nan Kim, Cheol-Hee Yu, Dae-Yeul |
author_sort | Han, Bing |
collection | PubMed |
description | Peroxiredoxin I (Prx I), an antioxidant enzyme, has multiple functions in human cancer. However, the role of Prx I in hepatic tumorigenesis has not been characterized. Here we investigated the relevance and underlying mechanism of Prx I in hepatic tumorigenesis. Prx I increased in tumors of hepatocellular carcinoma (HCC) patients that aligned with overexpression of oncogenic H-ras. Prx I also increased in H-ras(G12V) transfected HCC cells and liver tumors of H-ras(G12V) transgenic (Tg) mice, indicating that Prx I may be involved in Ras-induced hepatic tumorigenesis. When Prx I was knocked down or deleted in HCC-H-ras(G12V) cells or H-ras(G12V) Tg mice, cell colony or tumor formation was significantly reduced that was associated with downregulation of pERK pathway as well as increased intracellular reactive oxygen species (ROS) induced DNA damage and cell death. Overexpressing Prx I markedly increased Ras downstream pERK/FoxM1/Nrf2 signaling pathway and inhibited oxidative damage in HCC cells and H-ras(G12V) Tg mice. In this study, we found Nrf2 was transcriptionally activated by FoxM1, and Prx I was activated by the H-ras(G12V)/pERK/FoxM1/Nrf2 pathway and suppressed ROS-induced hepatic cancer-cell death along with formation of a positive feedback loop with Ras/ERK/FoxM1/Nrf2 to promote hepatic tumorigenesis. |
format | Online Article Text |
id | pubmed-5356538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53565382017-03-24 Peroxiredoxin I is important for cancer-cell survival in Ras-induced hepatic tumorigenesis Han, Bing Shin, Hye-Jun Bak, In Seon Bak, Yesol Jeong, Ye-Lin Kwon, Taeho Park, Young-Ho Sun, Hu-Nan Kim, Cheol-Hee Yu, Dae-Yeul Oncotarget Research Paper Peroxiredoxin I (Prx I), an antioxidant enzyme, has multiple functions in human cancer. However, the role of Prx I in hepatic tumorigenesis has not been characterized. Here we investigated the relevance and underlying mechanism of Prx I in hepatic tumorigenesis. Prx I increased in tumors of hepatocellular carcinoma (HCC) patients that aligned with overexpression of oncogenic H-ras. Prx I also increased in H-ras(G12V) transfected HCC cells and liver tumors of H-ras(G12V) transgenic (Tg) mice, indicating that Prx I may be involved in Ras-induced hepatic tumorigenesis. When Prx I was knocked down or deleted in HCC-H-ras(G12V) cells or H-ras(G12V) Tg mice, cell colony or tumor formation was significantly reduced that was associated with downregulation of pERK pathway as well as increased intracellular reactive oxygen species (ROS) induced DNA damage and cell death. Overexpressing Prx I markedly increased Ras downstream pERK/FoxM1/Nrf2 signaling pathway and inhibited oxidative damage in HCC cells and H-ras(G12V) Tg mice. In this study, we found Nrf2 was transcriptionally activated by FoxM1, and Prx I was activated by the H-ras(G12V)/pERK/FoxM1/Nrf2 pathway and suppressed ROS-induced hepatic cancer-cell death along with formation of a positive feedback loop with Ras/ERK/FoxM1/Nrf2 to promote hepatic tumorigenesis. Impact Journals LLC 2016-08-10 /pmc/articles/PMC5356538/ /pubmed/27517622 http://dx.doi.org/10.18632/oncotarget.11172 Text en Copyright: © 2016 Han et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Han, Bing Shin, Hye-Jun Bak, In Seon Bak, Yesol Jeong, Ye-Lin Kwon, Taeho Park, Young-Ho Sun, Hu-Nan Kim, Cheol-Hee Yu, Dae-Yeul Peroxiredoxin I is important for cancer-cell survival in Ras-induced hepatic tumorigenesis |
title | Peroxiredoxin I is important for cancer-cell survival in Ras-induced hepatic tumorigenesis |
title_full | Peroxiredoxin I is important for cancer-cell survival in Ras-induced hepatic tumorigenesis |
title_fullStr | Peroxiredoxin I is important for cancer-cell survival in Ras-induced hepatic tumorigenesis |
title_full_unstemmed | Peroxiredoxin I is important for cancer-cell survival in Ras-induced hepatic tumorigenesis |
title_short | Peroxiredoxin I is important for cancer-cell survival in Ras-induced hepatic tumorigenesis |
title_sort | peroxiredoxin i is important for cancer-cell survival in ras-induced hepatic tumorigenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356538/ https://www.ncbi.nlm.nih.gov/pubmed/27517622 http://dx.doi.org/10.18632/oncotarget.11172 |
work_keys_str_mv | AT hanbing peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT shinhyejun peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT bakinseon peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT bakyesol peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT jeongyelin peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT kwontaeho peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT parkyoungho peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT sunhunan peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT kimcheolhee peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis AT yudaeyeul peroxiredoxiniisimportantforcancercellsurvivalinrasinducedhepatictumorigenesis |