AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling
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Jia Li1,*, Yuanwei Guo1,2,*, Lili Duan1,*, Xinglin Hu1,*, Xi Zhang1,3, Jian Hu1,2, Li Huang1,2, Rongzhang He1, Zheng Hu1, Weihao Luo1, Tan Tan1,2, Renbin Huang1, Duanfang Liao1,4, Yuan-Shan Zhu5 and Di-Xian Luo1,2
1Translational Medicine Institute, National & Local Joint Engineering Laboratory for High-throughput Molecular Diagnosis Technology, Affiliated to The First People’s Hospital of Chenzhou, University of South China, Chenzhou 423000, P.R. China
2Center for Clinical Pathology, Affiliated to The First People’s Hospital of Chenzhou 423000, P.R. China
3Department of Neurology, Affiliated to The First People’s Hospital of Chenzhou 423000, P.R. China
4School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, P.R. China
5Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China
*These authors have contributed equally to this work
Di-Xian Luo, email: email@example.com
Keywords: breast cancer, AKR1B10, ERK
Received: November 04, 2016 Accepted: March 01, 2017 Published: March 28, 2017
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.
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