Extracellular matrix proteins regulate epithelial-mesenchymal transition in mammary epithelial cells

Qike K. Chen, Kang Ae Lee, Derek C. Radisky, Celeste M. Nelson

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Mouse mammary epithelial cells undergo transdifferentiation via epithelial-mesenchymal transition (EMT) upon treatment with matrix metalloproteinase-3 (MMP3). In rigid microenvironments, MMP3 upregulates expression of Rac1b, which translocates to the cell membrane to promote induction of reactive oxygen species and EMT. Here we examine the role of the extracellular matrix (ECM) in this process. Our data show that the basement membrane protein laminin suppresses the EMT response in MMP3-treated cells, whereas fibronectin promotes EMT. These ECM proteins regulate EMT via interactions with their specific integrin receptors. α6-integrin sequesters Rac1b from the membrane and is required for inhibition of EMT by laminin. In contrast, α5-integrin maintains Rac1b at the membrane and is required for the promotion of EMT by fibronectin. Understanding the regulatory role of the ECM will provide insight into mechanisms underlying normal and pathological development of the mammary gland.

Original languageEnglish (US)
Pages (from-to)126-132
Number of pages7
JournalDifferentiation
Volume86
Issue number3
DOIs
StatePublished - Oct 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

Keywords

  • Cell shape
  • Integrin
  • LrECM
  • Mechanical stress

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