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

K. Mythreye, E. H. Knelson, C. E. Gatza, Michael Gatza, G. C. Blobe

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 trafficking regulates cell adhesion and fibronectin fibrillogenesis in epithelial cells, as well as α5 localization in breast cancer patients. We further demonstrate that increased TβRIII expression correlates with increased α5 localization at sites of cell-cell adhesion in breast cancer patients, while higher TβRIII expression is a strong predictor of overall survival in breast cancer patients. These data support a novel, clinically relevant role for TβRIII in regulating integrin α5 localization, reveal a novel crosstalk mechanism between the integrin and TGF-β superfamily signaling pathways and identify β-arrestin2 as a regulator of α5β1 trafficking.

Original languageEnglish (US)
Pages (from-to)1416-1427
Number of pages12
JournalOncogene
Volume32
Issue number11
DOIs
StatePublished - Mar 14 2013
Externally publishedYes

Fingerprint

Integrins
Epithelial Cells
Cell Adhesion
Breast Neoplasms
Fibronectins
Focal Adhesions
Cell Movement
Ligands
Survival
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Mythreye, K. ; Knelson, E. H. ; Gatza, C. E. ; Gatza, Michael ; Blobe, G. C. / TβRIII/β-arrestin2 regulates integrin α5β1 trafficking, function, and localization in epithelial cells. In: Oncogene. 2013 ; Vol. 32, No. 11. pp. 1416-1427.
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TβRIII/β-arrestin2 regulates integrin α5β1 trafficking, function, and localization in epithelial cells. / Mythreye, K.; Knelson, E. H.; Gatza, C. E.; Gatza, Michael; Blobe, G. C.

In: Oncogene, Vol. 32, No. 11, 14.03.2013, p. 1416-1427.

Research output: Contribution to journalArticle

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