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Disruption of gap junctions in toxicity and carcinogenicity
J Kevin Chipman1, Angela Mally, Gareth O Edwards
1School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. j.k.chipman@bham.ac.uk
Abstract:
Although the specific role of connexin-mediated gap junctional intercellular communication in the control of cell homeostasis, proliferation, and death are still not clear, several lines of evidence support these roles. The disturbance of this communication, through multiple mechanisms, may in the short term be a protective mechanism to limit the spread of toxicity in a tissue following chemical or radiation damage. However, sustained downregulation confers a loss of tumor-suppressive action. Consequently, connexin dysfunction has been associated with both the action of many carcinogens and being a feature of cancer per se. Connexins offer not only a target for cancer chemoprevention but also for exploitation in chemotherapy through the "bystander" effect.
Insights
Connexin gap junctions regulate cell functions, and their disruption can initially protect tissues but ultimately promote cancer. Targeting connexins offers new strategies for cancer prevention and treatment.
Area of Science:
- Cell biology
- Molecular biology
- Cancer research
Background:
- Connexin-mediated gap junctional intercellular communication (GJIC) is implicated in cell homeostasis, proliferation, and death.
- Evidence suggests GJIC plays a role in tissue protection against damage.
- Dysfunctional GJIC is linked to carcinogen action and cancer development.
Purpose of the Study:
- To explore the roles of connexin-mediated GJIC in cellular processes.
- To investigate the dual role of GJIC disturbance in tissue protection and cancer progression.
- To highlight connexins as potential targets for cancer chemoprevention and chemotherapy.
Main Methods:
- Review of existing literature on connexins and GJIC.
- Analysis of mechanisms underlying GJIC disturbance.
- Examination of the link between GJIC and carcinogenesis.
Main Results:
- GJIC is crucial for maintaining cell homeostasis, proliferation, and survival.
- Short-term disruption of GJIC may offer transient tissue protection.
- Sustained downregulation of GJIC leads to loss of tumor suppression and promotes cancer.
Conclusions:
- Connexin dysfunction is associated with carcinogens and cancer.
- Connexins represent a promising target for cancer chemoprevention.
- Exploiting connexins, particularly via the "bystander" effect, offers novel chemotherapy strategies.