Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Carcinogenesis. 2018 Apr 5;39(4):562-570. doi: 10.1093/carcin/bgx148.
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 α1 (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.
碳酸酐酶 2（CA2）在调节离子转运和 pH 平衡方面发挥着重要作用，参与许多生物学过程；然而，其在癌症中的作用尚不清楚。在这项研究中，我们确定了 CA2 在促进肝细胞癌（HCC）转移中的一个新功能。CA2 的表达在 Na+-K+-ATPase α1（ATP1A1）下调的 HCC 细胞中升高，并与 HCC 中的 ATP1A1 呈负相关。ATP1A1 作为癌蛋白，而 CA2 过表达通过逆转 HCC 中的上皮-间充质转化（EMT）抑制细胞迁移和侵袭。CA2 下调促进 HCC 转移和侵袭，而 ATP1A1 下调抑制 HCC 转移。由于 CA2 和 ATP1A1 在 HCC 中的作用相反，我们研究了它们相关性在 HCC 转移中的作用。CA2 减弱了 ATP1A1 在体内引发的肿瘤生长和 ATP1A1 在体外诱导的转移。综上所述，这些结果表明 CA2 作为 HCC 转移和 EMT 的抑制剂，与 HCC 患者的总生存（OS）相关。
