1. AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway
- Author
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Chun Cai, Chenfei Huang, Yuhong Wang, Dan Huang, Yi Shen, Krishna Rao, Duan-Fang Liao, Junfei Jin, Yiwen Bu, Steven J. Verhulst, Yu Cao, Yingchun He, and Deliang Cao
- Subjects
rac1 GTP-Binding Protein ,0301 basic medicine ,Delta Catenin ,Pathology ,medicine.medical_specialty ,Integrin ,Aldo-Keto Reductases ,Mice, Nude ,Breast Neoplasms ,Integrin alpha5 ,Metastasis ,Focal adhesion ,Mice ,03 medical and health sciences ,AKR1B10 ,0302 clinical medicine ,breast cancer metastasis ,Aldehyde Reductase ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Cell adhesion ,biology ,business.industry ,integrin α5 ,Catenins ,Cell migration ,medicine.disease ,Metastatic breast cancer ,Gene Expression Regulation, Neoplastic ,src-Family Kinases ,030104 developmental biology ,Oncology ,Focal Adhesion Kinase 1 ,030220 oncology & carcinogenesis ,Catenin ,δ-catenin ,Cancer research ,biology.protein ,Female ,business ,Rac1 ,Research Paper ,Signal Transduction ,Proto-oncogene tyrosine-protein kinase Src - 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 α5 and δ-catenin. Silencing of integrin α5 or δ-catenin eradicated the cell adhesion and migration enhanced by AKR1B10, both of which acted synergistically. In these cells, the integrin α5 mediated focal adhesion kinase (FAK) signaling pathway was activated by AKR1B10, which, along with δ-catenin, stimulated Rac1-mediated cell migration and movement. In human primary and lymph node metastatic breast cancer, AKR1B10, integrin α5 and δ-catenin were correlatively upregulated with r=0.645 (p
- Published
- 2016