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T?RIII/?-arrestin2 regulates integrin ?5?1 trafficking, function, and localization in epithelial cells.


ABSTRACT: The type III TGF-? receptor (T?RIII) is a ubiquitous co-receptor for TGF-? superfamily ligands with roles in suppressing cancer progression, in part through suppressing cell motility. Here we demonstrate that T?RIII promotes epithelial cell adhesion to fibronectin in a ?-arrestin2 dependent and TGF-?/BMP independent manner by complexing with active integrin ?5?1, and mediating ?-arrestin2-dependent ?5?1 internalization and trafficking to nascent focal adhesions. T?RIII-mediated integrin ?5?1 trafficking regulates cell adhesion and fibronectin fibrillogenesis in epithelial cells, as well as ?5 localization in breast cancer patients. We further demonstrate that increased T?RIII expression correlates with increased ?5 localization at sites of cell-cell adhesion in breast cancer patients, while higher T?RIII expression is a strong predictor of overall survival in breast cancer patients. These data support a novel, clinically relevant role for T?RIII in regulating integrin ?5 localization, reveal a novel crosstalk mechanism between the integrin and TGF-? superfamily signaling pathways and identify ?-arrestin2 as a regulator of ?5?1 trafficking.

SUBMITTER: Mythreye K 

PROVIDER: S-EPMC3835656 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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

Mythreye K K   Knelson E H EH   Gatza C E CE   Gatza M L ML   Blobe G C GC  

Oncogene 20120507 11


The type III TGF-β receptor (TβRIII) is a ubiquitous co-receptor for TGF-β superfamily ligands with roles in suppressing cancer progression, in part through suppressing cell motility. Here we demonstrate that TβRIII promotes epithelial cell adhesion to fibronectin in a β-arrestin2 dependent and TGF-β/BMP independent manner by complexing with active integrin α5β1, and mediating β-arrestin2-dependent α5β1 internalization and trafficking to nascent focal adhesions. TβRIII-mediated integrin α5β1 tra  ...[more]

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