Induced cortical tension restores functional junctions in adhesion-defective carcinoma cells

Nat Commun. 2017 Nov 28;8(1):1834. doi: 10.1038/s41467-017-01945-y.


Normal epithelial cells are stably connected to each other via the apical junctional complex (AJC). AJCs, however, tend to be disrupted during tumor progression, and this process is implicated in cancer dissemination. Here, using colon carcinoma cells that fail to form AJCs, we investigated molecular defects behind this failure through a search for chemical compounds that could restore AJCs, and found that microtubule-polymerization inhibitors (MTIs) were effective. MTIs activated GEF-H1/RhoA signaling, causing actomyosin contraction at the apical cortex. This contraction transmitted force to the cadherin-catenin complex, resulting in a mechanosensitive recruitment of vinculin to cell junctions. This process, in turn, recruited PDZ-RhoGEF to the junctions, leading to the RhoA/ROCK/LIM kinase/cofilin-dependent stabilization of the junctions. RhoGAP depletion mimicked these MTI-mediated processes. Cells that normally organize AJCs did not show such MTI/RhoA sensitivity. Thus, advanced carcinoma cells require elevated RhoA activity for establishing robust junctions, which triggers tension-sensitive reorganization of actin/adhesion regulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Actin Depolymerizing Factors / metabolism
  • Actins / metabolism
  • Actomyosin / metabolism
  • Adherens Junctions / metabolism*
  • Adherens Junctions / ultrastructure
  • Biomechanical Phenomena
  • Caco-2 Cells
  • Cadherins / metabolism
  • Cell Adhesion / physiology*
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Cytoskeletal Proteins / metabolism*
  • Epithelial Cells / metabolism
  • Guanine Nucleotide Exchange Factors / metabolism
  • HT29 Cells / cytology
  • HT29 Cells / drug effects
  • HT29 Cells / physiology*
  • Humans
  • Intercellular Junctions / physiology*
  • Lim Kinases / metabolism
  • Microtubules
  • Myosin Type II / metabolism
  • Nocodazole / pharmacology
  • Signal Transduction
  • Vinculin / metabolism
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism


  • Actin Depolymerizing Factors
  • Actins
  • Cadherins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Guanine Nucleotide Exchange Factors
  • VCL protein, human
  • Vinculin
  • Actomyosin
  • LIMK1 protein, human
  • Lim Kinases
  • rho-Associated Kinases
  • Myosin Type II
  • rhoA GTP-Binding Protein
  • Nocodazole