| First Author | Meyer AE | Year | 2014 |
| Journal | Mol Biol Cell | Volume | 25 |
| Issue | 15 | Pages | 2291-304 |
| PubMed ID | 24870032 | Mgi Jnum | J:215228 |
| Mgi Id | MGI:5604935 | Doi | 10.1091/mbc.E14-03-0825 |
| Citation | Meyer AE, et al. (2014) Role of TGF-beta receptor III localization in polarity and breast cancer progression. Mol Biol Cell 25(15):2291-304 |
| abstractText | 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-beta cell surface receptor (TbetaRIII) 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 TbetaRIII is basolaterally localized in polarized breast epithelial cells and that disruption of the basolateral targeting of TbetaRIII 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 TbetaRIII 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 TbetaRIII is critical for maintenance of epithelial cell polarity and phenotype and expand the mechanisms by which TbetaRIII prevents breast cancer initiation and progression. |
