PDF(Pubmed)
Abstract：
Syntaxin-6 (STX6), a protein of the syntaxin family, is located in the trans-Golgi network and is involved in a variety of intracellular membrane transport events. STX6 is overexpressed in different human malignant tumors. However, little is known about its exact function and molecular mechanism in hepatocellular carcinoma (HCC). In this study, we found that the expression of STX6 was significantly increased in HCC tissues and was associated with poor survival. Gain- and loss-of-function experiments showed that STX6 promotes cell proliferation and metastasis of HCC cells both in vitro and in vivo. Mechanistically, STX6 was negatively regulated by the upstream stimulatory factor 2 (USF2). In addition, STX6 facilitates the association of autophagosomes with lysosomes. Importantly, we demonstrated that STX6 overexpression, despite enhanced resistance to lenvatinib, sensitizes HCC cells to the autophagy activator rapamycin. This study revealed that, under the control of USF2, STX6 accelerates the degradation of microtubule-associated protein 1 light chain 3 beta (LC3) by promoting autophagic flux, ultimately promoting HCC progression. Collectively, we suggest that the USF2-STX6-LC3B axis is a potential therapeutic target in liver cancer.
摘要：
Syntaxin-6(STX6),突触素家族的一种蛋白质，位于跨高尔基体网络中，参与各种胞内膜运输事件。STX6在不同的人类恶性肿瘤中过表达。然而,对其在肝细胞癌（HCC）中的确切功能和分子机制知之甚少。在这项研究中,我们发现,STX6在HCC组织中的表达显著升高,且与患者生存率低相关.功能增益和功能丧失实验表明，STX6在体外和体内均可促进HCC细胞的细胞增殖和转移。机械上,STX6受上游刺激因子2(USF2)负调控。此外,STX6促进自噬体与溶酶体的结合。重要的是,我们证明了STX6过表达，尽管对乐伐替尼的耐药性增强，肝癌细胞对自噬激活剂雷帕霉素敏感。这项研究表明,在USF2的控制下,STX6通过促进自噬通量加速微管相关蛋白1轻链3β(LC3)的降解,最终促进HCC进展。总的来说，我们认为USF2-STX6-LC3B轴是肝癌的潜在治疗靶点.
