Integrin-Linked Kinase, ECM Composition, and Substrate Rigidity Regulate Focal Adhesion - Actin Coupling, Modulating Survival, Proliferation and Migration: Towards a Biophysical Cancer Biomarker
type: CreativeWork
description: The extracellular matrix (ECM) has been implicated in numerous physiological and pathogenic processes. Integrins are thought to be the primary receptors that cells use to transduce biochemical and physical signals from the ECM. Integrin - ligand binding is specific for ECM molecules and is regulated by specific protein-protein interactions that further regulate downstream cellular activity such as motility, survival, growth, and proliferation. Termed outside-in signaling, the engagement of integrins results in protein recruitment to sites of cell - ECM contacts known as focal adhesions. Focal adhesions (FAs) are central to cell spreading, motility, survival and growth and serve as both physical linkages between the ECM and cytoskeleton as well as signaling centers for a cell on 2D substrates. Termed focal adhesion-actin coupling, FAs physically link the cytoskeleton with the ECM via actin binding proteins and are involved in mechanically coupling the cell to the ECM. To date, FAs' signaling properties and FA- actin coupling have been unrelated and independent mechanisms. This study provides data that suggests the amount, or level, of focal adhesion coupling in addition to regulating traction force generation, motility events and the rigidity response, also regulates the amount of biochemical signaling towards survival, growth and proliferation. First, via a knockout cell line system I demonstrate that Integrin-Linked Kinase is involved in coupling Beta1 integrins to collagen and FAs. I then demonstrate that lack of coupling results in altered rigidity sensing, defects in spreading of the cytoplasm, lower force generation and collagen contraction, as well as altered localization and activation of MAP kinases. Specifically, when ILK null cells were plated on collagen coated glass they were unable to reinforce Beta1 integrin mediated interactions nor spread their cytoplasm or undergo contractile activity. In contrast, when ILK null cells were plated on fibronectin coat…
abstract: The extracellular matrix (ECM) has been implicated in numerous physiological and pathogenic processes. Integrins are thought to be the primary receptors that cells use to transduce biochemical and physical signals from the ECM. Integrin - ligand binding is specific for ECM molecules and is regulated by specific protein-protein interactions that further regulate downstream cellular activity such as motility, survival, growth, and proliferation. Termed outside-in signaling, the engagement of integrins results in protein recruitment to sites of cell - ECM contacts known as focal adhesions. Focal adhesions (FAs) are central to cell spreading, motility, survival and growth and serve as both physical linkages between the ECM and cytoskeleton as well as signaling centers for a cell on 2D substrates. Termed focal adhesion-actin coupling, FAs physically link the cytoskeleton with the ECM via actin binding proteins and are involved in mechanically coupling the cell to the ECM. To date, FAs' signaling properties and FA- actin coupling have been unrelated and independent mechanisms. This study provides data that suggests the amount, or level, of focal adhesion coupling in addition to regulating traction force generation, motility events and the rigidity response, also regulates the amount of biochemical signaling towards survival, growth and proliferation. First, via a knockout cell line system I demonstrate that Integrin-Linked Kinase is involved in coupling Beta1 integrins to collagen and FAs. I then demonstrate that lack of coupling results in altered rigidity sensing, defects in spreading of the cytoplasm, lower force generation and collagen contraction, as well as altered localization and activation of MAP kinases. Specifically, when ILK null cells were plated on collagen coated glass they were unable to reinforce Beta1 integrin mediated interactions nor spread their cytoplasm or undergo contractile activity. In contrast, when ILK null cells were plated on fibronectin coat…
author: Chander, Ashok Coil
language: English
keywords: Biology, Cytology, Biophysics
date published: 2012
date modified: 2026-07-24T01:44:18Z
provider: Columbia University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Columbia University

PropertyValue
property ID: DOI
value: 10.7916/D8ZW1SVS