The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma
The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma
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钾通道KCa3.1通过激活SKP2促进细胞增殖并通过EMT途径促进肝细胞癌转移
DOI：
10.1002/ijc.32121
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发表时间：
2019-07-15
影响因子：
6.4
通讯作者：
Song, Penghong
中科院分区：
文献类型：
--
作者：
Du, Yehui;Song, Wenfeng;Song, Penghong
中电导钙激活钾通道（KCa3.1）在维持细胞内钙稳态中起重要作用，并参与许多人类癌症的肿瘤发生。然而，KCa3.1是否在肝细胞癌（HCC）的发生中起作用尚不清楚，肝细胞癌是世界上最常见的恶性肿瘤之一，预后极差。在我们的研究中，我们发现与相邻的非癌组织相比，KCa3.1在低分化肝癌组织中的表达显著升高。体外和体内实验表明，KCa3.1能够促进肝癌细胞的增殖、迁移和侵袭。从机制上讲，KCa3.1通过激活S期蛋白激酶2（SKP2）触发p21和p27的降解来促进肝癌细胞的细胞周期进程，以及通过靶向Reelin（RELN）诱导上皮 - 间质转化（EMT）来分别促进肝癌细胞的迁移和侵袭。总之，我们的结果表明KCa3.1在肝癌的发生和进展中起重要作用，这意味着它可能是肝癌一个有前景的治疗靶点。
The intermediate conductance calcium-activated potassium channel (KCa3.1) plays an important role in maintaining intracellular calcium homeostasis and is involved in the tumorigenesis of many human cancers. However, it is unknown whether KCa3.1 plays a role in the genesis of hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide with a very poor prognosis. In our study, we found that the expression of KCa3.1 was significantly elevated in poorly differentiated HCC tissues compared to adjacent noncancerous tissues. In vitro and in vivo experiments showed that KCa3.1 could promote cell proliferation, migration, and invasion of HCC. Mechanistically, KCa3.1 promoted cell cycle progression and migration and invasion of HCC cells by activating S-phase protein kinase 2 (SKP2) to trigger the degradation of p21 and p27 and targeting Reelin (RELN) to induce epithelial-mesenchymal transition (EMT), respectively. Taken together, our results demonstrate that KCa3.1 plays an important role in the genesis and progression of HCC, implying that it might be a promising therapeutic target in HCC.