AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway

被引：29

作者：

Huang, Chenfei ^{[1
]}

Verhulst, Steven ^{[1
]}

Shen, Yi ^{[1
]}

Bu, Yiwen ^{[1
]}

Cao, Yu ^{[1
]}

He, Yingchun ^{[1
,2
]}

Wang, Yuhong ^{[2
]}

Huang, Dan ^{[2
]}

Cai, Chun ^{[2
]}

Rao, Krishna ^{[1
]}

Liao, Duan-Fang ^{[2
]}

Jin, Junfei ^{[3
]}

Cao, Deliang ^{[1
,2
]}

机构：

[1] Southern Illinois Univ, Simmons Canc Inst, Dept Med Microbiol Immunol & Cell Biol, Sch Med, Springfield, IL 62794 USA

[2] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China

[3] Guilin Med Univ, China USA Lipids Hlth & Dis Res Ctr, Guilin 541001, Guangxi, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 28期

基金：

中国国家自然科学基金;

关键词：

AKR1B10; breast cancer metastasis; integrin alpha 5; delta-catenin; Rac1; REDUCTASE FAMILY 1; DELTA-CATENIN; PROTEIN; B10; GROWTH; OVEREXPRESSION; MORPHOGENESIS; ALPHA; CELLS;

D O I：

10.18632/oncotarget.9672

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 alpha 5 and delta-catenin. Silencing of integrin alpha 5 or delta-catenin eradicated the cell adhesion and migration enhanced by AKR1B10, both of which acted synergistically. In these cells, the integrin alpha 5 mediated focal adhesion kinase (FAK) signaling pathway was activated by AKR1B10, which, along with d-catenin, stimulated Rac1-mediated cell migration and movement. In human primary and lymph node metastatic breast cancer, AKR1B10, integrin alpha 5 and delta-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 alpha and delta-catenin mediated FAK/Src/Rac1 signaling pathway.

引用

页码：43779 / 43791

页数：13

共 38 条

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