突触核蛋白γ（SNCG）除了在神经系统表达之外，也在包括肝癌在内的多种恶性肿瘤中表达。 SNCG表达水平与肿瘤转移密切相关，但其促转移的分子机制仍不明晰，有待于深入研究。原癌基因Twist1也促进肿瘤转移，同时也是转化生长因子-β (TGF-β) 信号通路中的重要因子。我们预实验发现TGF-β及Twist1均可诱导肝癌细胞中的SNCG表达, SNCG促进TGF-β及Twist1诱导肝癌细胞迁移、侵袭。因此，本课题拟深入研究SNCG在TGF-β信号转导及肝癌转移中的作用机制。主要内容包括TGF-β及Twist1对SNCG表达的调控作用及机制、抑制Twist1或SNCG表达对TGF-β诱导肝癌细胞迁移与侵袭的影响、SNCG对TGF-β诱导的非SMAD信号通路的影响及机制、抑制SNCG表达对TGF-βRI与Twist1诱导肝癌转移的影响等。该研究对深入揭示SNCG在肿瘤进展中的功能具有重要意义。

γ-Synuclein (SNCG) is not only expressed in nervous system, but also overexpressed in a variety of human cancer including liver cancer. Overexpression of SNCG significantly correlates with cancer metastasis, while the mechanisms underlying the promotion of cancer metastasis by SNCG remain elusive. Therefore, it warrants further study to reveal the mechanisms for the tumor-promoting effects of SNCG. As a proto-oncogene and an effector in TGF-β signaling, Twist1 also promotes cancer metastasis. Our preliminary data reveal that SNCG can be induced by both TGF-β and Twist1 in liver cancer cells. Moreover, SNCG promotes TGF-β- and Twist1-induced liver cancer cell migration and invasion. Thus, the current project aims to investigate roles of SNCG in TGF-β signaling and HCC metastasis. We will investigate the regulation of SNCG expression by TGF-β and Twist1, the effects of Twist1 or SNCG knockdown on TGF-β-induced HCC cell migration and invasion, the effects of SNCG on non-SMAD TGF-β signaling and the effect of SNCG knockdown on TGF-βR- or Twist1-induced cancer metastasis, etc. This project may provide important insights into the functions of SNCG in cancer progression.