Abstract

This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new integrin adhesions. This mechanism operates in addition to local cytoskeletal remodeling triggered by conformational changes in the E-cadherin-associated protein α-catenin, at sites of mechanical perturbation. Studies using magnetic twisting cytometry (MTC), together with traction force microscopy (TFM) and confocal imaging identified force-activated E-cadherin-specific signals that integrate cadherin force transduction, integrin activation and cell contractility. EGFR is required for the downstream activation of PI3K and myosin-II-dependent cell stiffening. Our findings also demonstrated that α-catenin-dependent cytoskeletal remodeling at perturbed E-cadherin adhesions does not require cell stiffening. These results broaden the repertoire of E-cadherin-based force transduction mechanisms, and define the force-sensitive signaling network underlying the mechano-chemical integration of spatially segregated adhesion receptors.

Original languageEnglish (US)
Pages (from-to)1843-1854
Number of pages12
JournalJournal of cell science
Volume129
Issue number9
DOIs
StatePublished - May 1 2016

Keywords

  • Cell signaling
  • E-cadherin
  • Integrin
  • Magnetic twisting cytometry
  • Mechanotransduction
  • Traction force microscopy

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'E-cadherin-mediated force transduction signals regulate global cell mechanics'. Together they form a unique fingerprint.

  • Cite this