Gap Junction Intercellular Communication Positively Regulates Cisplatin Toxicity by Inducing DNA Damage through
Sanjeevani Arora1, Joshua R Heyza2, Elaine C Chalfin3
1Department of Cancer Biology, University of Toledo Health Science Campus, Toledo, OH 43614, USA. sanjeevani.arora@fccc.edu.
Cancers
|October 4, 2018
Summary
Cisplatin
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- The radiation-induced bystander effect (RIBE) involves gap junction intercellular communication (GJIC).
- Cisplatin cytotoxicity may also be influenced by functional GJIC.
Purpose of the Study:
- To investigate the role of GJIC in cisplatin-induced cytotoxicity and bystander effects.
- To determine if GJIC enhances cisplatin's DNA-damaging effects.
Main Methods:
- Utilized lung and ovarian cancer cell lines.
- Manipulated gap junction formation by targeting GJA1/Connexin 43 (Cx43).
- Assessed DNA double-strand breaks (DSBs) via γH2AX formation.
- Employed a cisplatin-DNA adduct specific antibody.
- Studied cisplatin response in ERCC1-XPF deficient cells.
Main Results:
- Cisplatin cytotoxicity is density-dependent and mediated by GJIC.
- Targeting Cx43 or preventing gap junction formation confers cisplatin resistance.
- Cisplatin induces DNA DSBs in bystander cells via GJIC.
- Cisplatin itself is not the signal transmitted through gap junctions.
- ERCC1-XPF deficient cells show increased sensitivity to cisplatin with GJIC.
Conclusions:
- Gap junction intercellular communication enhances cisplatin cytotoxicity.
- GJIC plays a significant role in mediating cisplatin's DNA-damaging bystander effects.
Keywords:
ERCC1-XPFbystander effectchemoresistancecisplatinconnexin 43gap junctiongap junction intercellular communicationMore Related Videos
09:47An Iodide-Yellow Fluorescent Protein-Gap Junction-Intercellular Communication Assay
Published on: February 1, 2019
7.6K
09:52A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication
Published on: September 20, 2016
10.9K
Related Concept Videos
02:09Bystander Effect
10.3K
The discussion of bullying highlights the problem of witnesses not intervening to help a victim. This is a common occurrence, as the following well-publicized event demonstrates. In 1964, in Queens, New York, a 19-year-old woman named Kitty Genovese was attacked by a person with a knife near the back entrance to her apartment building and again in the hallway inside her apartment building. When the attack occurred, she screamed for help numerous times and eventually died from her stab wounds.
10.3K
01:27Gap Junctions
9.6K
The cytoplasm of adjacent animal cells can exchange small molecules, ions, and secondary messengers via the communication channels which form the gap junctions. These junctions comprise a few hundred to thousands of molecular channels, each made of two halves, called the connexon hemichannel. A connexon is a hexamer of six transmembrane connexin proteins, which assemble radially, thus forming a pore or channel in the center. One connexon hemichannel docks with a corresponding connexon on the...
9.6K
01:37Gap Junctions
57.2K
Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...
57.2K
02:03What is Cell Signaling?
130.9K
Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
130.9K
01:45Positive Regulator Molecules
136.4K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
136.4K
02:39Positive Regulator Molecules
6.9K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.9K