Tissue geometry patterns epithelial-mesenchymal transition via intercellular mechanotransduction

Esther W. Gomez, Qike K. Chen, Nikolce Gjorevski, Celeste M. Nelson

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Epithelial-mesenchymal transition (EMT) is a phenotypic change in which epithelial cells detach from their neighbors and become motile. Whereas soluble signals such as growth factors and cytokines are responsible for stimulating EMT, here we show that gradients of mechanical stress define the spatial locations at which EMT occurs. When treated with transforming growth factor (TGF)-β, cells at the corners and edges of square mammary epithelial sheets expressed EMT markers, whereas those in the center did not. Changing the shape of the epithelial sheet altered the spatial pattern of EMT. Traction force microscopy and finite element modeling demonstrated that EMT-permissive regions experienced the highest mechanical stress. Myocardin-related transcription factor (MRTF)-A was localized to the nuclei of cells located in high-stress regions, and inhibiting cytoskeletal tension or MRTF-A expression abrogated the spatial patterning of EMT. These data suggest a causal role for tissue geometry and endogenous mechanical stresses in the spatial patterning of EMT.

Original languageEnglish (US)
Pages (from-to)44-51
Number of pages8
JournalJournal of cellular biochemistry
Volume110
Issue number1
DOIs
StatePublished - May 1 2010

Fingerprint

Epithelial-Mesenchymal Transition
Tissue
Geometry
Mechanical Stress
Transcription Factors
Transforming Growth Factors
Intercellular Signaling Peptides and Proteins
Microscopic examination
Cytokines
Atomic Force Microscopy
Traction
Cell Nucleus
Breast
Epithelial Cells
myocardin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Gomez, Esther W. ; Chen, Qike K. ; Gjorevski, Nikolce ; Nelson, Celeste M. / Tissue geometry patterns epithelial-mesenchymal transition via intercellular mechanotransduction. In: Journal of cellular biochemistry. 2010 ; Vol. 110, No. 1. pp. 44-51.
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Tissue geometry patterns epithelial-mesenchymal transition via intercellular mechanotransduction. / Gomez, Esther W.; Chen, Qike K.; Gjorevski, Nikolce; Nelson, Celeste M.

In: Journal of cellular biochemistry, Vol. 110, No. 1, 01.05.2010, p. 44-51.

Research output: Contribution to journalArticle

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