Overexpression of syntenin enhances hepatoma cell proliferation and invasion: Potential roles in human hepatoma
Overexpression of syntenin enhances hepatoma cell proliferation and invasion: Potential roles in human hepatoma
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Syntenin 过度表达增强肝癌细胞增殖和侵袭：在人肝癌中的潜在作用
DOI：
10.3892/or.2014.3498
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发表时间：
2014-12-01
期刊：
影响因子：
4.2
通讯作者：
Shi, Jianhua
中科院分区：
文献类型：
--
作者：
Liu, Xuemin;Zhang, Xufeng;Shi, Jianhua
肝细胞癌（HCC）是全球肿瘤相关死亡的第三大原因。最近，syntenin被发现在几种肿瘤中上调，并在癌症的发展中发挥关键作用。然而，其在肝细胞癌中的功能和潜在机制仍有待确定。在本研究中，syntenin的mRNA和蛋白质的表达水平在四个肝癌细胞系中检测到的升高。过表达syntenin促进肝癌细胞增殖。此外，syntenin上调增加表皮生长因子受体（EGFR）的表达，这占syntenin诱导的细胞增殖的先决条件与EGFR siRNA明显减弱syntenin转染细胞的细胞增殖。同时，syntenin过表达促进MMP-2的细胞侵袭，因为用抗MMP-2抗体预处理阻断了syntenin诱导的侵袭细胞数量。此外，syntenin上调诱导p38 MAPK的磷酸化，从而导致MMP-2表达的增加，因为用p38 MAPK的特异性抑制剂（SB 203580）处理明显废除了syntenin诱导的MMP-2表达。总的来说，我们的研究结果表明，syntenin过表达在促进肝癌细胞的增殖和侵袭中起着至关重要的作用。因此，本研究为syntenin如何加速肝癌的发生和发展提供了新的见解，并表明syntenin可能是一种有前途的抗肝癌治疗剂。
Hepatocellular carcinoma (HCC) ranks as the third leading cause of tumor-related mortality worldwide. Recently, syntenin was found to be upregulated in several tumors and to exert pivotal roles in the development of cancer. However, its function and the underlying mechanism in HCC remain to be defined. In the present study, the elevated expression levels of syntenin mRNA and protein were detected in four HCC cell lines. Overexpression of syntenin in hepatoma HCCLM3 cells enhanced cell proliferation. Furthermore, syntenin upregulation increased epidermal growth factor receptor (EGFR) expression, which accounted for syntenin-induced cell proliferation as precondition with EGFR siRNA clearly attenuated cell proliferation in syntenin-transfected cells. At the same time, syntenin overexpression promoted cell invasion by MMP-2, as pretreatment with anti-MMP-2 antibody blocked syntenin-induced invading cell numbers. Additionally, syntenin upregulation induced the phosphorylation of p38 MAPK contributing to the increase in MMP-2 expression, as treatment with the specific inhibitor for p38 MAPK (SB203580) clearly abrogated MMP-2 expression induced by syntenin. Collectively, our results suggest that syntenin overexpression plays a critical role in promoting the proliferation and invasion of hepatoma cells. Therefore, the present study provides new insight into how syntenin accelerates the development and progression of hepatoma, and suggests that syntenin may be a promising therapeutic agent against hepatoma.