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

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...

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Autores principales: Huang, Chenfei, Verhulst, Steven, Shen, Yi, Bu, Yiwen, Cao, Yu, He, Yingchun, Wang, Yuhong, Huang, Dan, Cai, Chun, Rao, Krishna, Liao, Duan-Fang, Jin, Junfei, Cao, Deliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190059/
https://www.ncbi.nlm.nih.gov/pubmed/27248472
http://dx.doi.org/10.18632/oncotarget.9672
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author Huang, Chenfei
Verhulst, Steven
Shen, Yi
Bu, Yiwen
Cao, Yu
He, Yingchun
Wang, Yuhong
Huang, Dan
Cai, Chun
Rao, Krishna
Liao, Duan-Fang
Jin, Junfei
Cao, Deliang
author_facet Huang, Chenfei
Verhulst, Steven
Shen, Yi
Bu, Yiwen
Cao, Yu
He, Yingchun
Wang, Yuhong
Huang, Dan
Cai, Chun
Rao, Krishna
Liao, Duan-Fang
Jin, Junfei
Cao, Deliang
author_sort Huang, Chenfei
collection PubMed
description 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<0.0001) and r=0.796 (p<0.0001), respectively. These data suggest that AKR1B10 promotes breast cancer metastasis through activation of the integrin α5 and δ-catenin mediated FAK/Src/Rac1 signaling pathway.
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spelling pubmed-51900592017-01-05 AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway Huang, Chenfei Verhulst, Steven Shen, Yi Bu, Yiwen Cao, Yu He, Yingchun Wang, Yuhong Huang, Dan Cai, Chun Rao, Krishna Liao, Duan-Fang Jin, Junfei Cao, Deliang Oncotarget Research Paper 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<0.0001) and r=0.796 (p<0.0001), respectively. These data suggest that AKR1B10 promotes breast cancer metastasis through activation of the integrin α5 and δ-catenin mediated FAK/Src/Rac1 signaling pathway. Impact Journals LLC 2016-05-27 /pmc/articles/PMC5190059/ /pubmed/27248472 http://dx.doi.org/10.18632/oncotarget.9672 Text en Copyright: © 2016 Huang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Huang, Chenfei
Verhulst, Steven
Shen, Yi
Bu, Yiwen
Cao, Yu
He, Yingchun
Wang, Yuhong
Huang, Dan
Cai, Chun
Rao, Krishna
Liao, Duan-Fang
Jin, Junfei
Cao, Deliang
AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway
title AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway
title_full AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway
title_fullStr AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway
title_full_unstemmed AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway
title_short AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway
title_sort akr1b10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated fak/src/rac1 signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190059/
https://www.ncbi.nlm.nih.gov/pubmed/27248472
http://dx.doi.org/10.18632/oncotarget.9672
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