Related Experiment Video

Updated: Aug 18, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Activation of the small GTPase Rac is sufficient to disrupt cadherin-dependent cell-cell adhesion in normal human

V M Braga1, M Betson, X Li

  • 1Medical Research Council Laboratory for Molecular Cell Biology and the Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom. v.braga@ucl.ac.uk

Molecular Biology of the Cell
|November 10, 2000
PubMed

Insights

Sustained Rac activation disrupts epithelial cell adhesion by disassembling cadherin complexes, a process distinct from lamellipodia formation. This Rac activity may coordinate cell adhesion changes during tumor progression.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Epithelial cells rely on specialized adhesive structures for tissue integrity.
  • Tumor progression involves breakdown of cell adhesion and acquisition of a fibroblastic, metastatic phenotype.
  • Ras transformation and Rac signaling pathways are implicated in disrupting cadherin-dependent adhesion.

Purpose of the Study:

  • To investigate if sustained Rac activation alone can disassemble cadherin-mediated cell-cell contacts.
  • To determine the specific mechanisms and cellular processes involved in Rac-induced adhesion breakdown.
  • To explore Rac's role in coordinating cell-cell and cell-substratum adhesion during tumorigenesis.

Main Methods:

  • Experiments involving sustained Rac activation in keratinocytes.
  • Time- and concentration-dependent analysis of cadherin and integrin receptor localization at cell junctions.
  • Mapping of the Rac protein region responsible for junction disruption.
  • Comparison of cadherin disassembly with Rac-dependent lamellipodia formation.

Main Results:

  • Sustained Rac activation is sufficient to disassemble cadherin-mediated contacts in a dose- and time-dependent manner.
  • Cadherin receptors are removed from junctions preceding integrin receptors, indicating specific interference with cadherin function.
  • A specific region in the Rac protein's effector domain was identified as crucial for junction disassembly.
  • Cadherin complex disassembly by Rac is a novel activity, separate from lamellipodia formation.

Conclusions:

  • Rac signaling directly impacts epithelial cell-cell adhesion by disassembling cadherin complexes.
  • This Rac-mediated disruption of adhesion is a distinct cellular process from lamellipodia formation.
  • Rac's dual role in cell adhesion and migration positions it as a key regulator in tumorigenesis and metastasis.

More Related Videos

Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound08:51

Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound

Published on: May 8, 2012

Comparing the Affinity of GTPase-binding Proteins using Competition Assays10:37

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

Related Concept Videos

Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...