TβRIII/β-arrestin2 regulates integrin α5β1 trafficking, function, and localization in epithelial cells

被引：22
作者：
Mythreye, K. [1 ]
Knelson, E. H. [2 ]
Gatza, C. E. [1 ]
Gatza, M. L. [3 ]
Blobe, G. C. [1 ,2 ]
机构：
[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27708 USA
[2] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27708 USA
[3] Duke Univ, Med Ctr, Duke IGSP, Durham, NC 27708 USA
来源：
ONCOGENE | 2013年 / 32卷 / 11期
关键词：
integrin alpha 5 beta 1; beta-arrestin2; TGF-beta; betaglycan; TGF-BETA RECEPTOR; FOCAL ADHESION KINASE; CANCER; BETAGLYCAN; PROTEIN; ALPHA-V-BETA-3; EXPRESSION; MEMBRANE; BINDING; INVASIVENESS;
D O I：
10.1038/onc.2012.157
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The type III TGF-beta receptor (T beta RIII) is a ubiquitous co-receptor for TGF-beta superfamily ligands with roles in suppressing cancer progression, in part through suppressing cell motility. Here we demonstrate that T beta RIII promotes epithelial cell adhesion to fibronectin in a beta-arrestin2 dependent and TGF-beta/BMP independent manner by complexing with active integrin alpha 5 beta 1, and mediating beta-arrestin2-dependent alpha 5 beta 1 internalization and trafficking to nascent focal adhesions. T beta RIII-mediated integrin alpha 5 beta 1 trafficking regulates cell adhesion and fibronectin fibrillogenesis in epithelial cells, as well as alpha 5 localization in breast cancer patients. We further demonstrate that increased T beta RIII expression correlates with increased alpha 5 localization at sites of cell-cell adhesion in breast cancer patients, while higher T beta RIII expression is a strong predictor of overall survival in breast cancer patients. These data support a novel, clinically relevant role for T beta RIII in regulating integrin alpha 5 localization, reveal a novel crosstalk mechanism between the integrin and TGF-beta superfamily signaling pathways and identify beta-arrestin2 as a regulator of alpha 5 beta 1 trafficking. Oncogene (2013) 32, 1416-1427; doi:10.1038/onc.2012.157; published online 7 May 2012
引用
收藏
页码：1416 / 1427
页数：12
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