SENP1 regulates hepatocyte growth factor-induced migration and epithelial-mesenchymal transition of hepatocellular carcinoma
SENP1 regulates hepatocyte growth factor-induced migration and epithelial-mesenchymal transition of hepatocellular carcinoma
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SENP1 调节肝细胞生长因子诱导的肝细胞癌迁移和上皮间质转化。
DOI：
10.1007/s13277-015-4406-y
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发表时间：
2016-06-01
期刊：
影响因子：
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通讯作者：
Wang, Lisheng
中科院分区：
文献类型：
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作者：
Zhang, Wenwen;Sun, Huiyan;Wang, Lisheng
HGF/c-Met信号通路的失调与上皮-间质转化（EMT）和肝细胞癌（HCC）的发生发展有关。然而，HGF/c-Met调控HCC细胞EMT和转移的表观遗传学机制尚不清楚。在这项研究中，我们证明了肝癌细胞表达高水平的SUMO/sentrin特异性蛋白酶1（Senp 1），这是由HGF/c-Met信号诱导的。慢病毒介导的小发夹RNA（shRNA）转导导致肝癌细胞中Senp 1沉默。Senp 1沉默降低HGF诱导的HCC细胞增殖和迁移。Senp 1抑制还诱导HCC细胞凋亡和生长停滞。此外，Senp 1基因敲低抑制上皮-间质转化，E-cadherin和ZO-1表达增加，FN和N-cadherin表达减少。EMT相关转录因子Zeb 1在Senp 1沉默的HCC细胞中被SUMO修饰并减少。提示senp 1可能在HGF诱导的肝癌细胞侵袭和迁移中起重要作用。
The deregulation of HGF/c-Met signaling is implicated in epithelial-mesenchymal transition (EMT) and progress of hepatocellular carcinoma (HCC). However, the epigenetic mechanisms that HGF/c-Met regulates EMT and metastasis of HCC cells are less explored. In this study, we demonstrated that HCC cells express a high level of SUMO/sentrin-specific protease 1 (Senp1) which is induced by HGF/c-Met signals. Lentivirus-mediated small hairpin RNA (shRNA) transduction results in Senp1 silence in HCC cells. Senp1 silence reduces the HGF-induced proliferation and migration of HCC cells. Senp1 inhibition also induces HCC cell apoptosis and growth arrest. Furthermore, Senp1 knockdown inhibits epithelial-to-mesenchymal transition, with increase of E-cadherin and ZO-1 expression, decrease of fibronectin and N-cadherin expression. The EMT-related transcription factor Zeb1 was SUMO-modified and decreased in Senp1-silenced HCC cells. These results delineate that senp1 might play an important role in the regulation of HGF-induced invasion and migration of HCC cells.