Gap Junction Intercellular Communication in the Carcinogenesis Hallmarks: Is This a Phenomenon or Epiphenomenon?
Abstract
:1. Introduction
- Hallmarks of cancer are: “acquired functional capabilities that allow cancer cells to survive, proliferate, and disseminate; these functions are acquired in different tumor types via distinct mechanisms and at various times during the course of multistep tumorigenesis” [19];
- GJIC is the major mechanism used by biological systems enabling cells to work in an integrate way;
- Epiphenomenon is a phenomenon that occurs contemporary to another but is not related to it [20].
Gap Junctions, Hemichannels, and Connexins
2. GJ, GJIC, and Cancer
Carcinogenesis Models and Cancer Hallmarks
- (1)
- Self-sufficiency in growth signals (later renamed proliferative signaling)—i.e., cancer cells grow at a seemingly unlimited rate.
- (2)
- Insensitivity to antigrowth signals (evading growth suppressors)—i.e., cancer cells are not subject to antigrowth signals nor withdrawal of normal growth signals.
- (3)
- Evading apoptosis (resisting cell death)—i.e., cancer cells avoid the usual process, whereby abnormal or redundant cells trigger internal self-destroying (as opposed to cell death) mechanisms.
- (4)
- Limitless replicative potential (enabling replicative immortality)—i.e., cancer cells do not senesce (or age) and die after a limited number of cell divisions.
- (5)
- Sustained angiogenesis (inducing angiogenesis)—i.e., cancer cells elicit new blood vessels to sustain growth.
- (6)
- Tissue invasion and metastasis (activating invasion and metastasis)—i.e., in situ or non-invasive cancers grow into pre-existing spaces, but invasive tumors must create a space to expand into normal tissue.
3. GJIC and Hallmarks of Cancer
3.1. “Insensitivity to Antigrowth Signals” and “Sustaining Proliferative Signaling”
3.2. Dysregulating Metabolism
3.3. Evading Apoptosis
3.4. Enabling Replicative Immortality
3.5. Inducing Angiogenesis
3.6. Activating Invasion and Metastasis
3.7. Avoiding Immune Destruction
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Zefferino, R.; Piccoli, C.; Di Gioia, S.; Capitanio, N.; Conese, M. Gap Junction Intercellular Communication in the Carcinogenesis Hallmarks: Is This a Phenomenon or Epiphenomenon? Cells 2019, 8, 896. https://doi.org/10.3390/cells8080896
Zefferino R, Piccoli C, Di Gioia S, Capitanio N, Conese M. Gap Junction Intercellular Communication in the Carcinogenesis Hallmarks: Is This a Phenomenon or Epiphenomenon? Cells. 2019; 8(8):896. https://doi.org/10.3390/cells8080896
Chicago/Turabian StyleZefferino, Roberto, Claudia Piccoli, Sante Di Gioia, Nazzareno Capitanio, and Massimo Conese. 2019. "Gap Junction Intercellular Communication in the Carcinogenesis Hallmarks: Is This a Phenomenon or Epiphenomenon?" Cells 8, no. 8: 896. https://doi.org/10.3390/cells8080896