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.
K E Y W O R D SAKT, EVA1, HCC, metastasis, PIK3R3
| INTRODUC TI ONHepatocellular carcinoma (HCC) is the fifth most common type of malignant tumor and a leading cause of cancer-related death worldwide. 1 HCC is a complex malignancy with various genetic abnormalities. Although HCC patients can be treated by surgical resection, radiotherapy and/or sorafenib, many HCC patients die due to recurrence, metastasis and blood vessel invasion. [2][3][4] Therefore, exploring the molecular mechanism of HCC tumorigenesis and metastasis may help to understand the pathogenesis of HCC and to find potential molecular targets for treatment of this malignancy.This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.