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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 β1-chain-derived fragment interacts via α3β1-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 α3β1-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.

Original publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





5908 - 5913


Animals, Basigin, Binding Sites, Cadherins, Cell Adhesion, Embryonic Stem Cells, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Humans, Integrin alpha3beta1, Laminin, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Mice, Peptide Fragments, Protein Binding, Signal Transduction, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2