TableEdit

Medici, D and Nawshad, A (2010) Type I collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of NF-kappaB and LEF-1. Matrix Biol. 29:161-5

Collagen I has been shown to promote epithelial-mesenchymal transition (EMT), a critical process of embryonic development and disease progression. However, little is known about the signaling mechanisms by which collagen I induces this cellular transformation. Here we show that collagen I causes ILK-dependent phosphorylation of IkappaB and subsequent nuclear translocation of active NF-kappaB, which in turn promotes increased expression of the Snail and LEF-1 transcription factors. ILK also causes inhibitory phosphorylation of GSK-3beta, a kinase that prevents functional activation of both Snail and LEF-1. These transcription factors alter expression of epithelial and mesenchymal markers to initiate EMT and stimulate cell migration. These data provide a foundation for understanding the mechanisms by which collagen I stimulates EMT and identify potential therapeutic targets for suppressing this transition in pathological conditions.

PubMed PMC2849845 Online version:10.1016/j.matbio.2009.12.003

Cell Line, Tumor; Cell Movement/physiology; Collagen Type I/physiology; Epithelial Cells/metabolism; Epithelial Cells/pathology; Extracellular Matrix/physiology; Humans; Immunoblotting; Immunohistochemistry; Lymphoid Enhancer-Binding Factor 1/genetics; Lymphoid Enhancer-Binding Factor 1/physiology; Mesoderm/metabolism; Mesoderm/pathology; NF-kappa B/genetics; NF-kappa B/physiology; Phosphorylation; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/physiology; RNA, Small Interfering/administration & dosage; RNA, Small Interfering/genetics; Transcription Factors/genetics; Transcription Factors/physiology