| First Author | Shintani Y | Year | 2006 |
| Journal | Mol Biol Cell | Volume | 17 |
| Issue | 7 | Pages | 2963-75 |
| PubMed ID | 16624865 | Mgi Jnum | J:112742 |
| Mgi Id | MGI:3663260 | Doi | 10.1091/mbc.E05-12-1123 |
| Citation | Shintani Y, et al. (2006) Phosphoinositide-3 kinase-Rac1-c-Jun NH2-terminal kinase signaling mediates collagen I-induced cell scattering and up-regulation of N-cadherin expression in mouse mammary epithelial cells. Mol Biol Cell 17(7):2963-75 |
| abstractText | During epithelial-to-mesenchymal transitions (EMTs), cells must change their interactions with one another and with their extracellular matrix in a synchronized manner. To characterize signaling pathways cells use to coordinate these changes, we used NMuMG mammary epithelial cells. We showed that these cells become fibroblastic and scattered, with increased N-cadherin expression when cultured on collagen I. Rac1 and c-Jun NH2-terminal kinase (JNK) were activated when cells were plated on collagen I, and dominant inhibitory Rac1 (RacN17) or inhibition of JNK signaling prevented collagen I-induced morphological changes and N-cadherin up-regulation. Furthermore, inhibiting phosphoinositide-3 kinase (PI3K) activity prevented Rac1 and JNK activation as well as collagen I-induced N-cadherin up-regulation. These data implicate PI3K-Rac1-JNK signaling in collagen I-induced changes in NMuMG cells. To establish a role for N-cadherin in collagen I-induced cell scattering, we generated N-cadherin overexpressing and knockdown NMuMG cells and showed that knocking down N-cadherin expression prevented collagen I-induced morphological changes. Motility assays showed that cells overexpressing N-cadherin were significantly more motile than mock-transfected cells and that N-cadherin-mediated motility was collagen I dependent. In addition, we showed that cord formation and branching in three-dimensional culture (EMT-dependent events) required N-cadherin expression and PI3K-Rac1-JNK signaling. |
