Back to Search
Start Over
Role of TGF-β receptor III localization in polarity and breast cancer progression.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2014 Aug 01; Vol. 25 (15), pp. 2291-304. Date of Electronic Publication: 2014 May 28. - Publication Year :
- 2014
-
Abstract
- The majority of breast cancers originate from the highly polarized luminal epithelial cells lining the breast ducts. However, cell polarity is often lost during breast cancer progression. The type III transforming growth factor-β cell surface receptor (TβRIII) functions as a suppressor of breast cancer progression and also regulates the process of epithelial-to-mesenchymal transition (EMT), a consequence of which is the loss of cell polarity. Many cell surface proteins exhibit polarized expression, being targeted specifically to the apical or basolateral domains. Here we demonstrate that TβRIII is basolaterally localized in polarized breast epithelial cells and that disruption of the basolateral targeting of TβRIII through a single amino acid mutation of proline 826 in the cytosolic domain results in global loss of cell polarity through enhanced EMT. In addition, the mistargeting of TβRIII results in enhanced proliferation, migration, and invasion in vitro and enhanced tumor formation and invasion in an in vivo mouse model of breast carcinoma. These results suggest that proper localization of TβRIII is critical for maintenance of epithelial cell polarity and phenotype and expand the mechanisms by which TβRIII prevents breast cancer initiation and progression.<br /> (© 2014 Meyer et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)
- Subjects :
- Animals
Breast Neoplasms pathology
Cell Line, Tumor
Cell Movement
Cell Polarity
Cell Proliferation
Disease Progression
Epithelial Cells metabolism
Epithelial-Mesenchymal Transition
Female
Humans
Mice, Nude
Mutation, Missense
Neoplasm Transplantation
Protein Transport
Proteoglycans genetics
Receptors, Transforming Growth Factor beta genetics
Transforming Growth Factor beta physiology
Breast Neoplasms metabolism
Proteoglycans metabolism
Receptors, Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1939-4586
- Volume :
- 25
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 24870032
- Full Text :
- https://doi.org/10.1091/mbc.E14-03-0825