Abstract
Since their characterization more than five decades ago, gap junctions and their structural proteins—the connexins—have been associated with cancer cell growth. During that period, the accumulation of data and molecular knowledge about this association revealed an apparent contradictory relationship between them and cancer. It appeared that if gap junctions or connexins can down regulate cancer cell growth they can be also implied in the migration, invasion and metastatic dissemination of cancer cells. Interestingly, in all these situations, connexins seem to be involved through various mechanisms in which they can act either as gap-junctional intercellular communication mediators, modulators of signalling pathways through their interactome, or as hemichannels, which mediate autocrine/paracrine communication. This complex involvement of connexins in cancer progression is even more complicated by the fact that their hemichannel function may overlap with other gap junction-related proteins, the pannexins. Despite this complexity, the possible involvements of connexins and pannexins in cancer progression and the elucidation of the mechanisms they control may lead to use them as new targets to control cancer progression. In this review, the involvements of connexins and pannexins in these different topics (cancer cell growth, invasion/metastasis process, possible cancer therapeutic targets) are discussed.
Highlights
The majority of cancers in adults are solid tumours [1]
Whatever the models or the approaches, the global conclusion is that Cx expression/gap-junctional intercellular communication (GJIC) is inversely correlated to cell growth
In contrast to general belief of Panx channels in promoting cancer cell death, this paper suggests that adenosine triphosphate (ATP) release by Panx1 suppresses deformation-induced apoptosis through P2Y receptor signalling and inhibition of Panx1 channels could reduce the efficiency of breast cancer metastasis
Summary
The majority of cancers in adults are solid tumours [1]. Whatever their tissue origin, those tumours are characterized by two fundamental properties, which are, first, an uncontrolled cell proliferation forming the tumour itself and an acquired invasion capacity leading to the dissemination of cancer cells in the organism. Fifty years of investigation have shown involvement of gap junctions (GJs) or their molecular components, the connexins (Cxs), in these two fundamental characteristics of cancer progression [2,3,4]. Cxs may be involved in these mechanisms through their interactome to modulate signalling pathways [5] or by acting as hemichannels (Hcs) mediating autocrine/paracrine communication [6]. This last activity may overlap with pannexins (Panxs) which are Cx-related proteins (Figure 1) [7]. We will review the involvement of Cxs and Panxs in these different topics, which are cancer cell proliferation, invasion/metastasis process and as possible targets for cancer control
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