Connexins and Pannexins: Important Players in Tumorigenesis, Metastasis and Potential Therapeutics.
Connexins and Pannexins: Important Players in Tumorigenesis, Metastasis and Potential Therapeutics.
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DOI：
10.3390/ijms19061645
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发表时间：
2018-06-01
影响因子：
5.6
通讯作者：
Mesnil M
中科院分区：
文献类型：
--
作者：
Graham SV;Jiang JX;Mesnil M
自从五十多年前确定了它们的特征以来，缝隙连接及其结构蛋白--连接蛋白--一直与癌细胞的生长有关。在此期间，有关这种关联的数据和分子知识的积累揭示了它们与癌症之间明显的矛盾关系。研究表明，如果缝隙连接或连接蛋白可以下调癌细胞的生长，它们也可以参与癌细胞的迁移、侵袭和转移扩散。有趣的是，在所有这些情况下，连接蛋白似乎通过不同的机制参与其中，在这些机制中，它们既可以作为缝隙连接的细胞间通讯媒介，通过它们的互动体调节信号通路，也可以作为半通道，介导自分泌/旁分泌通讯。连接蛋白在癌症进展中的这种复杂参与甚至更加复杂，因为它们的半通道功能可能与其他缝隙连接相关蛋白--连接蛋白--重叠。尽管存在这种复杂性，但连接蛋白和连接蛋白在癌症进展中的可能参与及其控制机制的阐明可能导致将它们用作控制癌症进展的新靶点。本文就连接蛋白和连接蛋白在不同主题(癌细胞生长、侵袭/转移过程、可能的肿瘤治疗靶点)中的作用进行了讨论。
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.
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DOI：
10.1038/nrc.2016.105
发表时间：
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期刊：
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