title: AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling.
abstract: 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.
authors.affiliation: Translational 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Translational 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.|Center for Clinical Pathology, Affiliated to The First People's Hospital of Chenzhou 423000, P.R. China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Translational 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.
authors.forename: Lili
authors.initials: L
authors.lastname: Duan
authors.affiliation: Translational 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.
authors.forename: Xinglin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Translational 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.|Department of Neurology, Affiliated to The First People's Hospital of Chenzhou 423000, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Translational 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.|Center for Clinical Pathology, Affiliated to The First People's Hospital of Chenzhou 423000, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.affiliation: Translational 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.|Center for Clinical Pathology, Affiliated to The First People's Hospital of Chenzhou 423000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Translational 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.
authors.forename: Rongzhang
authors.initials: R
authors.lastname: He
authors.affiliation: Translational 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.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Translational 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.
authors.forename: Weihao
authors.initials: W
authors.lastname: Luo
authors.affiliation: Translational 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.|Center for Clinical Pathology, Affiliated to The First People's Hospital of Chenzhou 423000, P.R. China.
authors.forename: Tan
authors.initials: T
authors.lastname: Tan
authors.affiliation: Translational 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.
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
authors.affiliation: Translational 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.|School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, P.R. China.
authors.forename: Duanfang
authors.initials: D
authors.lastname: Liao
authors.affiliation: Department 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.
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zhu
authors.affiliation: Translational 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.|Center for Clinical Pathology, Affiliated to The First People's Hospital of Chenzhou 423000, P.R. China.
authors.forename: Di-Xian
authors.initials: DX
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D000074426:Aldo-Keto Reductase Family 1 member B10 / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging
chemical_list: D000074426:Aldo-Keto Reductase Family 1 member B10
keywords: AKR1B10; ERK; breast cancer