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AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling
BACKGROUND: Aldo-keto reductase family 1, member B10 (AKR1B10), is known to be significantly induced in the cells of various cancers such as breast cancer. However, the mechanisms of AKR1B10 promoting tumorigenesis in breast cancer remain unclear. In the present study, we demonstrated the potential...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464903/ https://www.ncbi.nlm.nih.gov/pubmed/28402270 http://dx.doi.org/10.18632/oncotarget.16624 |
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author | Li, Jia Guo, Yuanwei Duan, Lili Hu, Xinglin Zhang, Xi Hu, Jian Huang, Li He, Rongzhang Hu, Zheng Luo, Weihao Tan, Tan Huang, Renbin Liao, Duanfang Zhu, Yuan-Shan Luo, Di-Xian |
author_facet | Li, Jia Guo, Yuanwei Duan, Lili Hu, Xinglin Zhang, Xi Hu, Jian Huang, Li He, Rongzhang Hu, Zheng Luo, Weihao Tan, Tan Huang, Renbin Liao, Duanfang Zhu, Yuan-Shan Luo, Di-Xian |
author_sort | Li, Jia |
collection | PubMed |
description | BACKGROUND: Aldo-keto reductase family 1, member B10 (AKR1B10), is known to be significantly induced in the cells of various cancers such as breast cancer. However, the mechanisms of AKR1B10 promoting tumorigenesis in breast cancer remain unclear. In the present study, we demonstrated the potential role and mechanism of AKR1B10 in the invasion and migration of breast cancer cells. METHODS: The expression level of AKR1B10 in breast carcinoma, para-carcinoma and cancer tissues were detected by immunohistochemical evaluation and real-time polymerase chain reaction (RT-PCR), and the correlationships between AKR1B10 expression and clinicopathological features in breast cancer patients (n=131) were investigated. AKR1B10 was ectopically expressed in MCF-7 cells or silenced in BT-20 cells. The roles of AKR1B10 expression in the migration and invasion of MCF-7 cells and BT-20 cells were explored by wound healing assay, transwell migration assay and transwell matrigel invasion assay, and finally the activation level of extracellular signal-regulated kinase 1/2 (EKR1/2) activation and the expression level of matrix metalloproteinase-2 (MMP2) and vimentin in MCF-7 and BT-20 cells were measured by western blot. RESULTS: We found that AKR1B10 expression was increased in malignant tissues, which was correlated positively with tumor size, lymph node metastasis (p<0.05). MCF-7/AKR1B10 cells displayed a higher ability of migration (43.57±1.04%) compared with MCF-7/vector cells (29.12±1.34%) in wound healing assay, and the migrated cell number of MCF-7/AKR1B10 was more (418.43±9.62) than that of MCF-7/vector (222.43±17.75) in transwell migration assay without matrigel. We furtherly confirmed MCF-7/AKR1B10 cells invaded faster compared with MCF-7/vector cells by transwell matrigel invasion assay. Finally, we found AKR1B10 induced the migration and invasion of MCF-7 and BT-20 cells by activating EKR signaling, which promoted the expressions of MMP2 and vimentin. PD98059, a specific inhibitor of the activation of MEK, blocked the migration and invasion by inhibiting the expression of MMP2 and vimentin. CONCLUSIONS: AKR1B10 is overexpressed in breast cancer, and promotes the migration and invasion of MCF-7 and BT-20 cells by activating ERK signaling pathway. |
format | Online Article Text |
id | pubmed-5464903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54649032017-06-21 AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling Li, Jia Guo, Yuanwei Duan, Lili Hu, Xinglin Zhang, Xi Hu, Jian Huang, Li He, Rongzhang Hu, Zheng Luo, Weihao Tan, Tan Huang, Renbin Liao, Duanfang Zhu, Yuan-Shan Luo, Di-Xian Oncotarget Research Paper BACKGROUND: Aldo-keto reductase family 1, member B10 (AKR1B10), is known to be significantly induced in the cells of various cancers such as breast cancer. However, the mechanisms of AKR1B10 promoting tumorigenesis in breast cancer remain unclear. In the present study, we demonstrated the potential role and mechanism of AKR1B10 in the invasion and migration of breast cancer cells. METHODS: The expression level of AKR1B10 in breast carcinoma, para-carcinoma and cancer tissues were detected by immunohistochemical evaluation and real-time polymerase chain reaction (RT-PCR), and the correlationships between AKR1B10 expression and clinicopathological features in breast cancer patients (n=131) were investigated. AKR1B10 was ectopically expressed in MCF-7 cells or silenced in BT-20 cells. The roles of AKR1B10 expression in the migration and invasion of MCF-7 cells and BT-20 cells were explored by wound healing assay, transwell migration assay and transwell matrigel invasion assay, and finally the activation level of extracellular signal-regulated kinase 1/2 (EKR1/2) activation and the expression level of matrix metalloproteinase-2 (MMP2) and vimentin in MCF-7 and BT-20 cells were measured by western blot. RESULTS: We found that AKR1B10 expression was increased in malignant tissues, which was correlated positively with tumor size, lymph node metastasis (p<0.05). MCF-7/AKR1B10 cells displayed a higher ability of migration (43.57±1.04%) compared with MCF-7/vector cells (29.12±1.34%) in wound healing assay, and the migrated cell number of MCF-7/AKR1B10 was more (418.43±9.62) than that of MCF-7/vector (222.43±17.75) in transwell migration assay without matrigel. We furtherly confirmed MCF-7/AKR1B10 cells invaded faster compared with MCF-7/vector cells by transwell matrigel invasion assay. Finally, we found AKR1B10 induced the migration and invasion of MCF-7 and BT-20 cells by activating EKR signaling, which promoted the expressions of MMP2 and vimentin. PD98059, a specific inhibitor of the activation of MEK, blocked the migration and invasion by inhibiting the expression of MMP2 and vimentin. CONCLUSIONS: AKR1B10 is overexpressed in breast cancer, and promotes the migration and invasion of MCF-7 and BT-20 cells by activating ERK signaling pathway. Impact Journals LLC 2017-03-28 /pmc/articles/PMC5464903/ /pubmed/28402270 http://dx.doi.org/10.18632/oncotarget.16624 Text en Copyright: © 2017 Li et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Li, Jia Guo, Yuanwei Duan, Lili Hu, Xinglin Zhang, Xi Hu, Jian Huang, Li He, Rongzhang Hu, Zheng Luo, Weihao Tan, Tan Huang, Renbin Liao, Duanfang Zhu, Yuan-Shan Luo, Di-Xian AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling |
title | AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling |
title_full | AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling |
title_fullStr | AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling |
title_full_unstemmed | AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling |
title_short | AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling |
title_sort | akr1b10 promotes breast cancer cell migration and invasion via activation of erk signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464903/ https://www.ncbi.nlm.nih.gov/pubmed/28402270 http://dx.doi.org/10.18632/oncotarget.16624 |
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