Epithelial V-like antigen 1 promotes hepatocellular carcinoma growth and metastasis via the ERBB-PI3K-AKT pathway
Epithelial V-like antigen 1 promotes hepatocellular carcinoma growth and metastasis via the ERBB-PI3K-AKT pathway
复制标题
上皮V样抗原1通过ERBB-PI3K-AKT途径促进肝细胞癌生长和转移
DOI：
10.1111/cas.14331
复制
发表时间：
2020-05-01
期刊：
影响因子：
5.7
通讯作者：
Ma，Xingyuan
中科院分区：
文献类型：
--
作者：
Ni，QianZhi;Chen，Zhenhua;Ma，Xingyuan
上皮V样抗原1（EVA 1）在胸腺发育和稳态中的作用已得到充分研究;然而，其与癌症的假定关系在很大程度上仍然未知。因此，在这里，我们研究了EVA 1在肝细胞癌中的作用。有趣的是，EVA 1表达在肝细胞癌（HCC）中显著增加，并且还与HCC患者的不良预后和复发相关。在体外，EVA 1的过表达促进了细胞的生长、侵袭和迁移。因此，EVA 1表达的敲低在体外抑制了HCC细胞的增殖和迁移，同时在体内抑制了HCC细胞的转移。RNA-seq分析表明，EVA 1能够上调ERBB 3-PI 3 K通路中基因的表达。因此，在EVA 1过表达后的HCC细胞中检测到AKT磷酸化水平增加。PI 3 K抑制剂LY 294002可抑制AKT磷酸化并挽救EVA 1过表达的促肿瘤作用。总之，本研究揭示了EVA 1通过ERBB-PI 3 K-AKT信号通路在HCC进展和转移过程中的致癌作用，重申了EVA 1作为HCC治疗靶点和/或预后标志物的潜在用途。
The role of epithelial V‐like antigen 1 (EVA1) has been well studied in thymic development and homostasis; however, its putative relationship with cancer remains largely unknown. Therefore, here we investigated the role of EVA1 in hepatocellular carcinoma. Interestingly, EVA1 expression was significantly increased in hepatocellular carcinoma (HCC) and was also associated with a poor prognosis and recurrence in HCC patients. Overexpression of EVA1 promoted cell growth, invasion and migration in vitro. Consistently, knockdown of EVA1 expression inhibited proliferation and migration in vitro, while repressing metastasis of HCC cells in vivo. RNA‐seq analysis indicated that EVA1 is able to upregulate the expression of genes in the ERBB3‐PI3K pathway. Accordingly, an increased level of AKT phosphorylation was detected in HCC cells after EVA1 overexpression. LY294002, a PI3K inhibitor, inhibited AKT phosphorylation and rescued the tumor‐promoting effect of EVA1 overexpression. Altogether, the present study has revealed the oncogenic role of EVA1 during HCC progression and metastasis through the ERBB‐PI3K‐AKT signaling pathway, reiterating the potential use of EVA1 as a therapeutic target and/or prognostic marker for HCC.