AKR1B10 promotes breast cancer metastasis through integrin ?5/?-catenin mediated FAK/Src/Rac1 signaling pathway.

ABSTRACT: Aldo-keto reductase 1B10 (AKR1B10) is not expressed in normal breast, but upregulated in primary and metastatic breast cancers, being a negative prognostic factor. This study characterized the molecular mechanisms of AKR1B10-promoted breast cancer metastasis. Ectopic expression of AKR1B10 in breast cancer cells MCF-7 and MDA-MB-231 or siRNA-mediated silencing in BT-20 cells affected cell adhesion, migration and invasion in cell culture, and metastasis to the lung in the nude mice through upregulation of integrin ?5 and ?-catenin. Silencing of integrin ?5 or ?-catenin eradicated the cell adhesion and migration enhanced by AKR1B10, both of which acted synergistically. In these cells, the integrin ?5 mediated focal adhesion kinase (FAK) signaling pathway was activated by AKR1B10, which, along with ?-catenin, stimulated Rac1-mediated cell migration and movement. In human primary and lymph node metastatic breast cancer, AKR1B10, integrin ?5 and ?-catenin were correlatively upregulated with r=0.645 (p<0.0001) and r=0.796 (p<0.0001), respectively. These data suggest that AKR1B10 promotes breast cancer metastasis through activation of the integrin ?5 and ?-catenin mediated FAK/Src/Rac1 signaling pathway.

SUBMITTER: Huang C 

PROVIDER: S-EPMC5190059 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature