Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells

Celeste M. Nelson, Davitte Khauv, Mina J. Bissell, Derek C Radisky

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a "cuboidal" epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase-3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP-3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP-3/Rac1b-induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP-3. These effects are not caused by general disruptions in cell signaling pathways, as TGF-β-induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape-dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT-inducing agents.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalJournal of Cellular Biochemistry
Volume105
Issue number1
DOIs
StatePublished - Sep 1 2008

Fingerprint

Epithelial-Mesenchymal Transition
Cell Shape
Matrix Metalloproteinases
Breast
Epithelial Cells
Cell signaling
Matrix Metalloproteinase 3
Metabolism
Cells
Proteins
Cell Differentiation
Cell Count

Keywords

  • Cell morphology
  • Cell spreading
  • Epithelial-mesenchymal transition
  • Mammary epithelial cells
  • Matrix metalloproteinase
  • Micropatterned substrata
  • Rac1b
  • Reactive oxygen species
  • TGFβ

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells. / Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J.; Radisky, Derek C.

In: Journal of Cellular Biochemistry, Vol. 105, No. 1, 01.09.2008, p. 25-33.

Research output: Contribution to journalArticle

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