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Gap Junction Intercellular Communication in the Carcinogenesis Hallmarks: Is This a Phenomenon or Epiphenomenon?

1
Department of Medical and Surgical Sciences, University of Foggia, Via L. Pinto, 1-71122 Foggia, Italy
2
Department of Clinical and Experimental Medicine, University of Foggia, Via L. Pinto, 1-71122 Foggia, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(8), 896; https://doi.org/10.3390/cells8080896
Received: 3 July 2019 / Revised: 3 August 2019 / Accepted: 12 August 2019 / Published: 14 August 2019
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
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Abstract

If occupational tumors are excluded, cancer causes are largely unknown. Therefore, it appeared useful to work out a theory explaining the complexity of this disease. More than fifty years ago the first demonstration that cells communicate with each other by exchanging ions or small molecules through the participation of connexins (Cxs) forming Gap Junctions (GJs) occurred. Then the involvement of GJ Intercellular Communication (GJIC) in numerous physiological cellular functions, especially in proliferation control, was proven and accounts for the growing attention elicited in the field of carcinogenesis. The aim of the present paper is to verify and discuss the role of Cxs, GJs, and GJIC in cancer hallmarks, pointing on the different involved mechanisms in the context of the multi-step theory of carcinogenesis. Functional GJIC acts both as a tumor suppressor and as a tumor enhancer in the metastatic stage. On the contrary, lost or non-functional GJs allow the uncontrolled proliferation of stem/progenitor initiated cells. Thus, GJIC plays a key role in many biological phenomena or epiphenomena related to cancer. Depending on this complexity, GJIC can be considered a tumor suppressor in controlling cell proliferation or a cancer ally, with possible preventive or therapeutic implications in both cases. View Full-Text
Keywords: cancer; hallmark; connexins; microenvironment; inflammation; metastasis; angiogenesis; stem cells cancer; hallmark; connexins; microenvironment; inflammation; metastasis; angiogenesis; stem cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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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.

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