Collagen I promotes epithelial-to-mesenchymal transition in lung cancer cells via transforming growth factor-β signaling

Yasushi Shintani, Masato Maeda, Nina Chaika, Keith R. Johnson, Margaret J. Wheelock

Research output: Contribution to journalArticle

167 Scopus citations

Abstract

Epithelial-to-mesenchymal transition (EMT) is a fundamental biological process whereby epithelial cells lose their polarity and undergo a transition to a mesenchymal phenotype. When cancer cells invade adjacent tissues, they use a mechanism akin to EMT, and understanding the molecular mechanisms that drive this transition will facilitate studies into new targets for prevention of metastasis. Extracellular stimuli, such as growth factors, and their cytosolic effectors cooperate to promote EMT. In highly fibrotic cancers like lung cancer, it is thought that extracellular matrix molecules, including collagen, can initiate signals that promote EMT. Here, we present data showing that collagen I induces EMT in non-small cell lung cancer cell lines, which is prevented by blocking transforming growth factor (TGF)-β3 signaling. In addition, we show that collagen I-induced EMT is prevented by inhibitors of phosphoinositide 3-kinase and extracellular signal-related kinase signaling, which promotes transcription of TGF-β3 mRNA in these cells. Thus, our data are consistent with the hypothesis that collagen I induces EMT in lung cancer cells by activating autocrine TGF-β3 signaling. Epidermal growth factor also seems to initiate EMT via a TGF-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume38
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Cadherin switching
  • Collagen I
  • Epithelial-to-mesenchymal transition
  • Non-small cell lung cancer
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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