| First Author | Horejs CM | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 16 | Pages | 5908-13 |
| PubMed ID | 24706882 | Mgi Jnum | J:208874 |
| Mgi Id | MGI:5565136 | Doi | 10.1073/pnas.1403139111 |
| Citation | Horejs CM, et al. (2014) Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells. Proc Natl Acad Sci U S A 111(16):5908-13 |
| abstractText | The dynamic interplay between the extracellular matrix and embryonic stem cells (ESCs) constitutes one of the key steps in understanding stem cell differentiation in vitro. Here we report a biologically-active laminin-111 fragment generated by matrix metalloproteinase 2 (MMP2) processing, which is highly up-regulated during differentiation. We show that the beta1-chain-derived fragment interacts via alpha3beta1-integrins, thereby triggering the down-regulation of MMP2 in mouse and human ESCs. Additionally, the expression of MMP9 and E-cadherin is up-regulated in mouse ESCs-key players in the epithelial-to-mesenchymal transition. We also demonstrate that the fragment acts through the alpha3beta1-integrin/extracellular matrix metalloproteinase inducer complex. This study reveals a previously unidentified role of laminin-111 in early stem cell differentiation that goes far beyond basement membrane assembly and a mechanism by which an MMP2-cleaved laminin fragment regulates the expression of E-cadherin, MMP2, and MMP9. |
