Related Experiment Video

Updated: Apr 14, 2026

Invasion of Human Cells by a Bacterial Pathogen
07:15

Invasion of Human Cells by a Bacterial Pathogen

Published on: March 21, 2011

35.5K

Bacterial genotoxins promote inside-out integrin β1 activation, formation of focal adhesion complexes and cell

Laura Levi1, Tatsushi Toyooka1, Manuel Patarroyo2

  • 1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Plos One
|April 16, 2015
PubMed

Insights

Bacterial genotoxins activate integrin β1, enhancing cell adhesion and survival through an ATM-dependent pathway. This study reveals a novel cellular response to genotoxins, impacting cancer risk.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Integrins regulate cell adhesion, migration, survival, and proliferation.
  • Integrin role in genotoxic stress and bacterial toxin intoxication is poorly understood.
  • Bacterial genotoxins induce DNA damage and activate the DNA damage response (DDR) via ATM kinase.

Purpose of the Study:

  • Investigate integrin activation and its role in cell survival upon bacterial genotoxin exposure.
  • Elucidate the signaling pathways and molecular mechanisms involved in toxin-induced cellular responses.
  • Understand the implications for cancer initiation and progression.

Main Methods:

  • Exposure of cells to bacterial genotoxins.
  • Analysis of integrin β1 activation, focal adhesion assembly, and cell spreading.
  • Investigation of ATM-dependent signaling pathways.
  • Assessment of the roles of NET1, ALIX, and TSG101 in cellular responses.
  • Evaluation of anchorage-independent survival.

Main Results:

  • Bacterial genotoxins induce DNA damage, leading to integrin β1 activation.
  • Activated integrin β1 enhances cell spreading on fibronectin via ATM-dependent inside-out signaling.
  • The actin cytoskeleton regulator NET1 is essential for this phenotype.
  • Endosomal sorting complex required for transport (ESCRT) components ALIX and TSG101 are crucial for toxin-mediated cell spreading and survival.
  • Toxin-induced DNA damage promotes anchorage-independent cell survival.

Conclusions:

  • Bacterial genotoxins trigger a novel cellular response involving integrin β1 activation and enhanced cell survival.
  • ATM-dependent signaling and ESCRT machinery play critical roles in mediating these effects.
  • Findings provide insights into the carcinogenic potential of bacterial genotoxins in chronic infections.

More Related Videos

Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion09:56

Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion

Published on: February 11, 2022

3.2K
Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads07:55

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads

Published on: March 8, 2017

9.0K

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...
3.9K
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...
5.7K
Bacterial Toxins01:12

Bacterial Toxins

Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
95
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
6.2K
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
7.8K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
8.4K