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Chemical, oncogene and growth factor inhibition gap junctional intercellular communication: an integrative hypothesis
J E Trosko1, C C Chang, B V Madhukar
1Department of Pediatrics/Human Development, College of Human Medicine, Michigan State University, East Lansing.
Abstract:
Most, if not all, cancer cells have some dysfunction in gap-junction-mediated intercellular communication, either because of defects in cell adhesion or inability to have functional gap junctional communication. In addition, most, if not all, tumor-promoting chemicals and conditions down-regulate gap junction function, while some antitumor-promoting chemicals can up-regulate gap junctional communication. Several oncogenes are associated with down-regulation of gap junction function and several hormone and growth regulators, known to be tumor promoters, are also able to down-regulate gap junction function. On the other hand, some tumor suppressor genes have been linked to the up-regulation of gap junctions. Based on these observations, it is hypothesized that, if a progenitor cell is unable to perform gap junctional intercellular communication, normal growth control and cell differentiation would not be possible, thereby favoring the development of malignant neoplasia.
Insights
Cancer cells often show impaired gap junction communication, crucial for normal cell growth and differentiation. This dysfunction may be a key factor in the development of malignant neoplasia.
Area of Science:
- Cell Biology
- Oncology
- Molecular Biology
Background:
- Most cancer cells exhibit dysfunctional gap-junction-mediated intercellular communication.
- Tumor-promoting agents often down-regulate gap junction function, while some anti-tumor agents can up-regulate it.
Purpose of the Study:
- To investigate the role of gap junctional intercellular communication in cancer development.
- To explore the relationship between gap junction function and cellular growth control and differentiation.
Main Methods:
- Review of existing literature on gap junctions, oncogenes, tumor suppressors, and chemical/hormonal influences on cell communication.
- Analysis of the correlation between gap junction dysfunction and malignant neoplasia.
Main Results:
- Dysfunctional gap junctions are a common feature in cancer cells.
- Oncogenes and tumor promoters are frequently associated with down-regulation of gap junction function.
- Tumor suppressor genes are often linked to up-regulation of gap junctions.
Conclusions:
- Impaired gap junctional intercellular communication in progenitor cells may hinder normal growth control and differentiation.
- This inability to communicate intercellularly could predispose cells to developing malignant neoplasia.