Syntaxin-6 promotes the progression of hepatocellular carcinoma and alters its sensitivity to chemotherapies by activating the USF2/LC3B axis.
Syntaxin-6 promotes the progression of hepatocellular carcinoma and alters its sensitivity to chemotherapies by activating the USF2/LC3B axis.
复制标题
Syntaxin-6通过激活USF 2/LC 3B轴促进肝细胞癌的进展并改变其对化疗的敏感性。
DOI：
10.7150/ijbs.86636
复制
发表时间：
2023
影响因子：
9.2
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Zhou L;Wang Z;Chen X;Li X;Ge C;Min X;Zhao F;Chen T;Li J
语法6（STX6）是语法蛋白家族的蛋白质，位于反式高尔基网络中，参与各种细胞内膜转运事件。 STX6在不同的人类恶性肿瘤中过表达。然而，对于肝细胞癌（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HCC组织中STX6的表达显着增加，并且与存活率差有关。功能丧失的实验表明，STX6在体外和体内促进了HCC细胞的细胞增殖和转移。从机械上讲，STX6受到上游刺激因子2（USF2）负面调节。此外，STX6促进了自噬体与溶酶体的缔合。重要的是，我们证明了STX6的过表达尽管对Lenvatinib的抗性增强，但将HCC细胞敏感到自噬激活剂雷帕霉素。这项研究表明，在USF2的控制下，STX6通过促进自噬通量来加速微管相关蛋白1轻链3β（LC3）的降解，最终促进HCC的进展。总体而言，我们建议USF2-STX6-LC3B轴是肝癌中潜在的治疗靶标。
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.
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DOI：
10.1016/j.omto.2021.10.005
发表时间：
2021-12-17
期刊：
Molecular therapy oncolytics
影响因子：
--
作者：
Shi Y;Ye Z;Lu G;Yang N;Zhang J;Wang L;Cui J;Del Pozo MA;Wu Y;Xia D;Shen HM
通讯作者：
Shen HM
影响因子：
3.3
作者：
Davanger, S;Bock, JB;Scheller, RH
通讯作者：
Scheller, RH
影响因子：
4.3
作者：
Shitara, Akiko;Shibui, Toru;Okayama, Miki;Arakawa, Toshiya;Mizoguchi, Itaru;Shakakura, Yasunori;Takuma, Taishin
通讯作者：
Takuma, Taishin
影响因子：
7.4
作者：
Gao S;Zhang Z;Wang X;Ma Y;Li C;Liu H;Jing C;Li L;Guo X
通讯作者：
Guo X
SMURF1 泛素化 UVRAG 可促进自噬体成熟并抑制肝细胞癌生长
影响因子：
13.3
作者：
Feng, Xing;Jia, Yanyan;Zhang, Zhiyong
通讯作者：
Zhang, Zhiyong