Abstract
BackgroundAldo-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.MethodsThe 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.ResultsWe 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.ConclusionsAKR1B10 is overexpressed in breast cancer, and promotes the migration and invasion of MCF-7 and BT-20 cells by activating ERK signaling pathway.
Highlights
Breast cancer is the most common malignant tumor in female, and its incidence and mortality increased rapidly in recent decades
We found AKR1B10 induced the migration and invasion of MCF-7 and BT-20 cells by activating EKR signaling, which promoted the expressions of matrix metalloproteinase-2 (MMP2) and vimentin
Through statistically analyzing correlationships between AKR1B10 expression and clinicopathological parameters, we found the expression levels of AKR1B10 were highly positively correlated with tumor size and lymph node metastasis
Summary
Breast cancer is the most common malignant tumor in female, and its incidence and mortality increased rapidly in recent decades. Aldo-keto reductase family 1, member B10 (AKR1B10), is primarily expressed in human colon and small intestine but overexpressed in breast cancer, hepatocellular carcinoma, non-small cell lung carcinoma, cervical and endometrial cancers [2,3,4,5,6,7,8,9]. The molecular mechanisms of AKR1B10 promoting the metastasis of breast cancer remain largely unknown. Aldo-keto reductase family 1, member B10 (AKR1B10), is known to be significantly induced in the cells of various cancers such as breast cancer. The mechanisms of AKR1B10 promoting tumorigenesis in breast cancer remain unclear. We demonstrated the potential role and mechanism of AKR1B10 in the invasion and migration of breast cancer cells
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