AKR1B10 Promotes Breast Cancer Cell Migration And Invasion Via Activation Of ERK Signaling

Objective: Aldo-keto reductase family 1,member B10(AKR1B10),is known to be signifcantly 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.Materials and methods: At first,we collected wax samples of breast cancer tissues and para-carcinoma tissues from 131 breast cancer patients diagnosed with breast cancer during 2014 to 2016.Then detecting the AKR1B10 expression in breast cancer tissue by immunohistochemistry.Analysis of the correlation btween AKR1B10 expression levels and breast cancer tumor size,lymph node metastasis.The AKR1B10 gene was cloned into the endogenous non-expressing AKR1B10 breast cancer cell line(ie MCF-7)using a lentiviral system to establish a monoclonal cell line stablyexpressing AKR1B10(MCF-7/AKR1B10);silenced by siRNA knockdown plasmid endogenous AKR1B10-expressing BT20 cells;Western blot was used to detect total ERK protein levels;cell wound healing experiments,transwell migration assays and transwell matrigel invasion assays were used to investigate migration and invasion of MCF-7 cells and BT-20 cells effected by AKR1B10.At last,we detected the activation level of the extracellular signal-regulated kinase ERK1/2 of MCF-7 and BT-20 cells.The expression levels of matrix metalloproteinase-2(MMP2)and vimentin were detected 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 were proved a higher ability of migration(43.57±1.04%)compared with MCF-7/vector cells(29.12±1.34%)by wound healing assay,and the number of migrated MCF-7/AKR1B10 cell was larger(418.43±9.62)than that of MCF-7/vector(222.43±17.75)in transwell migration assay.A further transwell matrigel invasion assay was used to confirm MCF-7/AKR1B10 cells invaded faster than MCF-7/vector cell.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 specifc inhibitor of the activation of MEK,blocked the migration and invasion byinhibiting the expression of MMP2 and vimentin.Conclusion:1.AKR1B10 is highly expressed in breast cancer tissues,which is positively correlated with tumor size and lymph node metastasis;2.AKR1B10 activates ERK signaling pathway to promote migration and invasion of breast cancer cells;...