Fig. 6. Matrix signaling in EMT.
Type I collagen induces EMT through integrin or DDR1/2 signaling. Both types of receptors activate NF-κB and other transcription factors (TFs) that promote expression of SNAI1/2 and LEF1. Other pathways simplified here, such as those mediated by PI3K, ILK, proline-rich tyrosine kinase 2 (PYK2)–PDK1, and FAK-paxillin, are activated by type I collagen through integrins and DDRs, ultimately promoting the stabilization and activity of the EMT-associated transcription factors Snail1/2 and LEF-1. DDR1 is also known to form complexes with E-cadherin at the cell surface, which are disrupted upon binding to type I collagen.