Department of Medical and Surgical Sciences, University of Foggia, Via L. Pinto, 1-71122 Foggia, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, Via L. Pinto, 1-71122 Foggia, Italy.
Cells. 2019 Aug 14;8(8):896. doi: 10.3390/cells8080896.
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.
如果排除职业性肿瘤，癌症的病因在很大程度上是未知的。因此，制定一种理论来解释这种疾病的复杂性似乎是有用的。五十多年前，首次证明细胞通过连接蛋白（Cx）形成间隙连接（GJ）参与离子或小分子的交换来相互通讯。然后，GJ 细胞间通讯（GJIC）在许多生理细胞功能中的参与，特别是在增殖控制方面，得到了证实，并解释了在致癌发生领域引起的越来越多的关注。本文的目的是验证和讨论 Cx、GJ 和 GJIC 在癌症特征中的作用，并指出在多步骤致癌理论背景下不同的参与机制。功能性 GJIC 在转移阶段既是肿瘤抑制因子，也是肿瘤促进因子。相反，丧失或无功能的 GJ 允许起始细胞的不受控制的增殖。因此，GJIC 在与癌症相关的许多生物学现象或伴随现象中起着关键作用。根据这种复杂性，GJIC 可以被认为是控制细胞增殖的肿瘤抑制因子，或者是癌症的盟友，在这两种情况下都可能具有预防或治疗意义。
