AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway
| Autor: | 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, Deliang Cao |
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| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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