Carboxypeptidase A4 promotes proliferation and stem cell characteristics of hepatocellular carcinoma
Carboxypeptidase A4 promotes proliferation and stem cell characteristics of hepatocellular carcinoma
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DOI：
10.1111/iep.12315
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发表时间：
2019-04-01
影响因子：
3
通讯作者：
Li, Zhonglian
中科院分区：
文献类型：
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作者：
Zhang, Hongtao;Hao, Chengfei;Li, Zhonglian
羧肽酶A4（CPA4）是金属羧肽酶家族的一员，在肝癌中过度表达，并与癌症进展相关。CPA4在肝细胞癌（HCC）中的作用仍不清楚。在本研究中，我们旨在评估CPA4与肝癌细胞增殖及干细胞特性表达的相关性。蛋白质印迹分析显示，肝癌细胞系Bel7402中CPA4高表达，而在HepG2细胞中低表达。通过MTT和克隆形成实验检测到，CPA4的敲低降低了癌细胞的增殖。无血清培养系统显示，下调CPA4抑制了肿瘤细胞的球体形成能力。然而，上调CPA4增加了增殖和球体形成能力。此外，在CPA4上调的细胞中，CD133、ALDH1和CD44的蛋白表达也增加。在体内，将CPA4过表达的肿瘤细胞皮下注射到裸鼠中，显著增加了肿瘤的生长。这些数据表明，CPA4的表达通过调节肿瘤增殖和干细胞特性的表达导致不良预后，因此可能作为HCC的一个潜在治疗靶点。
Carboxypeptidase A4 (CPA4), a member of the metallo-carboxypeptidase family, is overexpressed in liver cancer and is associated with cancer progression. The role of CPA4 in hepatocellular carcinoma (HCC) remains unclear. In this study, we aimed to evaluate the relevance of CPA4 to the proliferation and expression of stem cell characteristics of hepatocellular carcinoma cells. Western blot analysis showed high CPA4 expression in the liver cancer cell line Bel7402 and low expression in HepG2 cells. Knock-down of CPA4 decreased cancer cell proliferation as detected by MTT and clone formation assays. The serum-free culture system revealed that downregulated CPA4 suppressed the sphere formation capacities of tumour cells. However, upregulated CPA4 increased the proliferation and sphere formation capacity. In addition, the protein expression of CD133, ALDH1 and CD44 also increased in cells with upregulated CPA4. In vivo, the overexpression of CPA4 in tumour cells that were subcutaneously injected into nude mice markedly increased the growth of the tumours. These data suggest that CPA4 expression leads to poor prognoses by regulating tumour proliferation and the expression of stem cell characteristics and may therefore serve as a potential therapeutic target of HCC.