Myosin light chain kinase mediates transcellular intravasation of breast cancer cells through the underlying endothelial cells: A three-dimensional FRET study

Satya Khuon, Luke Liang, Robert W. Dettman, Peter H.S. Sporn, Robert B. Wysolmerski, Teng Leong Chew*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

The transient and localized signaling events between invasive breast cancer cells and the underlying endothelial cells have remained poorly characterized. We report a novel approach integrating vascular engineering with three-dimensional time-lapse fluorescence resonance energy transfer (FRET) imaging to dissect how endothelial myosin light chain kinase (MLCK) is modulated during tumor intravasation. We show that tumor transendothelial migration occurs via both paracellular (i.e. through cell-cell junctions) and transcellular (i.e. through individual endothelial cells) routes. Endothelial MLCK is activated at the invasion site, leading to regional diphosphorylation of myosin-II regulatory light chain (RLC) and myosin contraction. Blocking endothelial RLC diphosphorylation blunts tumor transcellular, but not paracellular, invasion. Our results implicate an important role for endothelial myosin-II function in tumor intravasation.

Original languageEnglish (US)
Pages (from-to)431-440
Number of pages10
JournalJournal of cell science
Volume123
Issue number3
DOIs
StatePublished - Feb 1 2010

Keywords

  • Cytoskeletal signaling
  • Endothelium
  • FRET imaging
  • Transcellular invasion
  • Tumor intravasation
  • Vascular engineering

ASJC Scopus subject areas

  • Cell Biology

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