精氨酸琥珀酸合成酶 1 通过抑制肝癌中的 STAT3 通路抑制癌细胞侵袭。
Argininosuccinate synthase 1 suppresses cancer cell invasion by inhibiting STAT3 pathway in hepatocellular carcinoma.
机构信息
State Key Laboratory of Oncogenes and Related Genes, Department of Tumor Microenvironment, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
出版信息
Acta Biochim Biophys Sin (Shanghai). 2019 Mar 1;51(3):263-276. doi: 10.1093/abbs/gmz005.
Metastasis is the main reason for high recurrence and poor survival of hepatocellular carcinoma (HCC). The molecular mechanism underlying HCC metastasis remains unclear. In this study, we found that argininosuccinate synthase 1 (ASS1) expression was significantly decreased and down-regulation of ASS1 was closely correlated with poor prognosis in HCC patients. DNA methylation led to the down-regulation of ASS1 in HCC. Stable silencing of ASS1 promoted migration and invasion of HCC cells, whereas overexpression of ASS1-inhibited metastasis of HCC cells in vivo and in vitro. We also revealed that ASS1-knockdown increased the phosphorylation level of S727STAT3, which contributed to HCC metastasis by up-regulation of inhibitor of differentiation 1 (ID1). These findings indicate that ASS1 inhibits HCC metastasis and may serve as a target for HCC diagnosis and treatment.
转移是导致肝细胞癌（HCC）高复发和预后不良的主要原因。HCC 转移的分子机制尚不清楚。在本研究中，我们发现精氨琥珀酸合成酶 1（ASS1）的表达显著降低，ASS1 的下调与 HCC 患者的不良预后密切相关。DNA 甲基化导致 HCC 中 ASS1 的下调。ASS1 的稳定沉默促进 HCC 细胞的迁移和侵袭，而 ASS1 的过表达则抑制 HCC 细胞在体内和体外的转移。我们还揭示了 ASS1 敲低会增加 S727STAT3 的磷酸化水平，通过上调分化抑制因子 1（ID1）促进 HCC 转移。这些发现表明 ASS1 抑制 HCC 转移，可能成为 HCC 诊断和治疗的靶点。
Zotero 插件