Type I collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of NF-κB and LEF-1

Damian Medici, Ali Nawshad

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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 IκB and subsequent nuclear translocation of active NF-κB, which in turn promotes increased expression of the Snail and LEF-1 transcription factors. ILK also causes inhibitory phosphorylation of GSK-3β 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.

Original languageEnglish (US)
Pages (from-to)161-165
Number of pages5
JournalMatrix Biology
Volume29
Issue number3
DOIs
StatePublished - Apr 2010

Keywords

  • Collagen I
  • EMT
  • Epithelial-mesenchymal transition
  • ILK
  • LEF-1
  • NF-κB

ASJC Scopus subject areas

  • Molecular Biology

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