The cancer/testis antigen MAGEC2 promotes amoeboid invasion of tumor cells by enhancing STAT3 signaling
The cancer/testis antigen MAGEC2 promotes amoeboid invasion of tumor cells by enhancing STAT3 signaling
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癌症/睾丸抗原 MAGEC2 通过增强 STAT3 信号传导促进阿米巴对肿瘤细胞的侵袭
DOI：
10.1038/onc.2016.314
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发表时间：
2017-03-01
期刊：
影响因子：
8
通讯作者：
Yin, Y.
中科院分区：
文献类型：
--
作者：
Song, X.;Hao, J.;Yin, Y.
MAGEC2是一种在多种癌症中高度表达的癌/睾丸抗原，其生物学功能在很大程度上仍然未知。本研究表明，MAGEC2的表达在体外诱导肿瘤细胞的圆形形态和变形虫样运动，并促进肿瘤在体内的转移。MAGEC2的促转移作用是通过信号转导因子和转录激活因子3 （STAT3）激活介导的。在机制上，MAGEC2与STAT3相互作用，抑制肿瘤细胞核中STAT3的多泛素化和蛋白酶体降解，导致磷酸化STAT3的积累和转录活性增强。值得注意的是，MAGEC2和磷酸化STAT3的表达水平呈正相关，两者都与人肝细胞癌的转移发生率相关。本研究不仅揭示了MAGEC2在促进肿瘤转移中的作用，还发现了MAGEC2维持肿瘤细胞核中STAT3超激活的新的分子机制。因此，MAGEC2可能是治疗癌症的新的抗肿瘤转移靶点。
The biological function of MAGEC2, a cancer/testis antigen highly expressed in various cancers, remains largely unknown. Here we demonstrate that expression of MAGEC2 induces rounded morphology and amoeboid-like movement of tumor cells in vitro and promotes tumor metastasis in vivo. The pro-metastasis effect of MAGEC2 was mediated by signal transducer and activator of transcription 3 (STAT3) activation. Mechanistically, MAGEC2 interacts with STAT3 and inhibits the polyubiquitination and proteasomal degradation of STAT3 in the nucleus of tumor cells, resulting in accumulation of phosphorylated STAT3 and enhanced transcriptional activity. Notably, expression levels of MAGEC2 and phosphorylated STAT3 are positively correlated and both are associated with incidence of metastasis in human hepatocellular carcinoma. This study not only reveals a previously unappreciated role of MAGEC2 in promoting tumor metastasis, but also identifies a new molecular mechanism by which MAGEC2 sustains hyperactivation of STAT3 in the nucleus of tumor cells. Thus, MAGEC2 may represent a new antitumor metastasis target for treatment of cancer.