Related Experiment Video

Updated: Sep 20, 2026

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity
04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Modulation of DNA damage-induced apoptosis by cell adhesion is independently mediated by p53 and c-Abl

Tony Truong1, Guizhen Sun, Michael Doorly

  • 1Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 21, 2003
PubMed

Insights

Cell adhesion regulates cancer cell death. Integrin ligation activates the c-Abl/p73 pathway, enhancing chemotherapy effectiveness, particularly in p53-negative tumors.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Therapeutics

Background:

  • Conventional cancer therapies rely on DNA damage to induce tumor cell death.
  • Integrin-mediated adhesion loss can decrease apoptosis by reducing p53 levels after cell detachment.
  • Restoring integrin ligation can re-establish p53 levels and DNA damage sensitivity.

Purpose of the Study:

  • To investigate the role of c-Abl in regulating cancer cell killing by chemotherapy.
  • To determine if cell adhesion influences the c-Abl/p73 pathway's response to DNA damage.
  • To explore therapeutic strategies for enhancing chemotherapy in p53-negative tumors.

Main Methods:

  • Investigated the c-Abl tyrosine kinase activation in response to DNA damage and cell adhesion.
  • Assessed the adhesion-dependency of Abl-mediated p73 stabilization.
  • Evaluated the sensitivity of tumor cell lines to chemotherapy agents and an Abl inhibitor (STI571).

Main Results:

  • Cell adhesion is required for c-Abl tyrosine kinase activation by DNA damage.
  • c-Abl activation stabilizes p73, a proapoptotic factor, in an adhesion-dependent manner.
  • Tumor cell lines exhibit differential sensitivity to chemotherapy, suggesting varied reliance on p53 and c-Abl/p73 pathways.

Conclusions:

  • A second pathway involving c-Abl activation by DNA damage is regulated by cell adhesion.
  • Integrin ligation can activate the c-Abl/p73 pathway, enhancing chemotherapy efficacy.
  • Targeting integrin ligation may improve outcomes for p53-negative cancer patients.

More Related Videos

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

Related Concept Videos

DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...