Carbonic anhydrase 2 inhibits epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma
Carbonic anhydrase 2 inhibits epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma
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碳酸酐酶2抑制肝细胞癌上皮间质转化和转移
DOI：
10.1093/carcin/bgx148
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发表时间：
2018-04-01
期刊：
影响因子：
4.7
通讯作者：
Meng, Zhiqiang
中科院分区：
文献类型：
--
作者：
Zhang, Chenyue;Wang, Haiyong;Meng, Zhiqiang
碳酸酐酶2（Carbonic anhydrase 2，CA 2）在离子转运和pH平衡的调节中起重要作用，参与许多生物学过程，但其在癌症中的作用尚不清楚。在这项研究中，我们确定了一个新的功能，CA 2在促进肝细胞癌（HCC）转移。在Na+-K+-ATP酶α 1（ATP 1A 1）表达下调的HCC细胞中，CA 2表达升高，且与ATP 1A 1表达呈负相关。ATP 1A 1作为癌蛋白发挥作用，而CA 2过表达通过逆转HCC中上皮-间质转化（EMT）抑制细胞迁移和侵袭。CA 2下调促进肝癌的转移和侵袭，而ATP 1A 1下调抑制肝癌的转移。由于CA 2和ATP 1A 1在HCC中的相反作用，我们研究了它们在HCC转移中的相关性。CA 2在体内减弱ATP 1A 1触发的肿瘤生长和在体外减弱ATP 1A 1诱导的转移。综上所述，本研究结果表明，CA 2作为HCC转移和EMT的抑制因子，与HCC患者的良好总生存期（OS）相关。
Carbonic anhydrase 2 (CA2) plays vital role in the regulation of ion transport and pH balance and is involved in many biological processes; however, its role in cancer remains obscure. In this study, we identified a novel function of CA2 in facilitating hepatocellular carcinoma (HCC) metastasis. CA2 expression was elevated in Na+-K+-ATPase alpha 1 (ATP1A1)-downregulated HCC cells and was inversely correlated with that of ATP1A1 in HCC. ATP1A1 acted as an oncoprotein whereas CA2 overexpression inhibited cell migration and invasion by reversing epithelial-mesenchymal transition (EMT) in HCC. CA2 downregulation promoted HCC metastasis and invasion whereas ATP1A1 downregulation inhibited HCC metastasis. Because of the opposing effects of CA2 and ATP1A1 in HCC, we examined the role of their correlation in HCC metastasis. CA2 attenuated ATP1A1-triggered tumor growth in vivo and ATP1A1-induced metastasis in vitro. Taken together, the present results suggest that CA2 serves as a suppressor of HCC metastasis and EMT and is correlated with favorable overall survival (OS) in HCC patients.