Related Experiment Video

Updated: May 2, 2026

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress
10:57

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress

Published on: October 13, 2019

7.0K

Altering FAK-paxillin interactions reduces adhesion, migration and invasion processes

Thérèse B Deramaudt1, Denis Dujardin1, Fanny Noulet1

  • 1CNRS, UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Illkirch, France; Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.

Plos One
|March 20, 2014
PubMed

Insights

Targeting focal adhesion kinase (FAK) interactions with paxillin disrupts FAK localization and downstream signaling, inhibiting cell migration and invasion. This approach offers a novel strategy for developing FAK inhibitors.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Focal adhesion kinase (FAK) is crucial for integrin-mediated cell adhesion and signaling.
  • FAK plays a significant role in cancer metastasis, including cell adhesion, migration, and invasion.
  • Existing small molecule inhibitors target FAK's catalytic activity.

Purpose of the Study:

  • To investigate if inhibiting FAK's targeting to focal adhesions (FAs) is an effective strategy to block downstream pathways.
  • To explore the impact of disrupting FAK-paxillin interactions on FAK signaling and cellular functions.

Main Methods:

  • Constructed a FAK mutant unable to bind paxillin using mutagenesis.
  • Analyzed FAK localization, phosphorylation, and downstream target phosphorylation.
  • Assessed FA dynamics, cell adhesion, migration, and invasion capabilities.

Main Results:

  • The FAK mutant failed to localize to FAs, reducing FAK and target phosphorylation (paxillin, p130Cas).
  • FA dynamics were altered, leading to inhibited cell adhesion, migration, and invasion.
  • Cells expressing the FAK mutant showed reduced migration compared to FAK-/- cells, with decreased phospho-Src and phospho-p130Cas at FAs.

Conclusions:

  • Targeting FAK-paxillin interactions effectively reduces FAK signaling.
  • Disrupting FAK localization to FAs is a viable strategy to inhibit FAK downstream pathways.
  • This interaction represents a promising target for novel FAK inhibitor development.

More Related Videos

In vitro Cell Migration and Invasion Assays09:55

In vitro Cell Migration and Invasion Assays

Published on: June 1, 2014

140.2K
Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

6.2K

Related Concept Videos

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...
2.8K
Adherens Junctions01:24

Adherens Junctions

Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
5.8K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.5K
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
2.7K
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
4.3K
Anchoring Junctions01:03

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
4.3K