Connexins in Cancer: Jekyll or Hyde?

Connexins in Cancer: Jekyll or Hyde?
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癌症中的连接蛋白:Jekyll还是Hyde?

DOI:
10.3390/biom10121654
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发表时间:
2020-12-10
期刊:
影响因子:
5.5
通讯作者:
Lathia JD
Lathia JD
中科院分区:
生物学2区
文献类型:
--
作者:
Mulkearns-Hubert EE;Reizes O;Lathia JD

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连接蛋白(一种构成间隙连接的蛋白质亚基)的表达、定位和功能在癌症中经常发生改变。除了通过间隙连接通道进行细胞-细胞耦合外,连接蛋白还形成半通道,允许细胞与细胞外空间之间的通信并执行非连接的细胞内活动。历史上,连接蛋白被认为是肿瘤抑制因子;然而,在某些情况下,它们也可以起到促进肿瘤的作用。在这里,我们从连接蛋白的特定功能方面回顾了有关癌细胞中连接蛋白的文献,并提出连接蛋白在大多数(如果不是全部)癌症标志的上游起作用。先进的连接蛋白靶向方法的发展仍然是该领域进一步询问连接蛋白在癌症表型中的作用的机会,特别是通过使用体内模型。更多特异性的连接蛋白功能调节剂将有助于阐明连接蛋白在癌症中的功能,并在临床中推进连接蛋白特异性治疗。
The expression, localization, and function of connexins, the protein subunits that comprise gap junctions, are often altered in cancer. In addition to cell–cell coupling through gap junction channels, connexins also form hemichannels that allow communication between the cell and the extracellular space and perform non-junctional intracellular activities. Historically, connexins have been considered tumor suppressors; however, they can also serve tumor-promoting functions in some contexts. Here, we review the literature surrounding connexins in cancer cells in terms of specific connexin functions and propose that connexins function upstream of most, if not all, of the hallmarks of cancer. The development of advanced connexin targeting approaches remains an opportunity for the field to further interrogate the role of connexins in cancer phenotypes, particularly through the use of in vivo models. More specific modulators of connexin function will both help elucidate the functions of connexins in cancer and advance connexin-specific therapies in the clinic.
间隙连接和癌症:沟通50年。
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