A new perspective of mechanosensitive pannexin-1 channels in cancer metastasis: clues for the treatment of other stress-induced diseases.
A new perspective of mechanosensitive pannexin-1 channels in cancer metastasis: clues for the treatment of other stress-induced diseases.
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DOI：
10.1093/abbs/gmw018
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发表时间：
2016-05
影响因子：
3.7
通讯作者：
Di Wu;Lanfang Li;Linxi Chen
中科院分区：
文献类型：
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作者：
Di Wu;Lanfang Li;Linxi Chen
肿瘤转移是指癌细胞偏离原发部位，扩散到其他区域形成新的集落的过程，是导致癌症患者死亡的主要原因。在转移过程中，循环中的癌细胞停留在终末器官的微血管内，其中大多数死于机械变形。然而，癌细胞可以通过未知的机制从机械变形中存活下来。最近，Furlow et al.[1]Identifi获得突变截短形式的Pannexin-1(Panx-1)，Panx1 1-89，其在高转移癌细胞中显著富含fi。Panx1 1-89可增加Panx-1通道介导的三磷酸腺苷的释放，并通过促进转移性乳腺癌细胞在物理变形过程中的存活来提高转移的fi效率。此外，PANX-1的抑制剂甘苯氧酮(Cbx)被证明可以降低乳腺癌转移的fi率。这些结果提示，Panx-1是微血管生物力学损伤中转移细胞存活的分子基础之一[1]。2000年，包括Panx-1、Panx-2和Panx-3在内的三个Pannexins成员被发现是缝隙连接家族的新成员[2]。Panx-1在人体组织中广泛表达。后续的研究进一步表明，Panx-1形成连接细胞内和细胞外的单通道膜通道，而不是形成细胞间通道
Cancer metastasis is a process that cancer cells deviate from the pri-mary site and spread to the other areas to form new colonies, which is the leading cause of death in cancer patients. During metastatic progression, circulating cancer cells lodge within the microvasculature of end organs, where most of them die from mechanical deformation. However, cancer cells can survive from mechanical deformation by unknown mechanisms. Recently, Furlow et al . [1] identi fi ed a mutation truncated form of pannexin-1 (Panx-1), PANX1 1 – 89 , which was signi fi cantly enriched in highly metastatic cancer cells. PANX1 1 – 89 augmented Panx-1 channel-mediated adenosine triphosphate (ATP) release and enhanced the ef fi ciency of metastasis by promoting metastatic breast cancer cells survival during physical deformation. Add-itionally, carbenoxolone (CBX), a Panx-1 inhibitor, was proved to reduce the ef fi ciency of breast cancer metastasis. These results sug-gested that Panx-1 is one of the molecular bases for metastatic cell survival in microvasculature-induced biomechanical trauma [1]. In 2000, three members of pannexins, including Panx-1, Panx-2, and Panx-3, have been found to be new members of gap-junctions ’ family [2]. Panx-1 was ubiquitously expressed in human tissues. Sub-sequent studies further revealed that Panx-1 forms single-pass membrane channels that connect the intracellular and extracellular compartments rather than forming intercellular channels