TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradation.
TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradation.
复制标题
TRIM50 通过直接靶向 SNAIL 进行普遍降解来抑制肝癌进展。
DOI：
10.1038/s41419-018-0644-4
复制
发表时间：
2018-05-22
影响因子：
9
通讯作者：
Han L
中科院分区：
文献类型：
--
作者：
Ma X;Ma X;Qiu Y;Zhu L;Lin Y;You Y;Ma D;Qin Z;Sun C;Zhao Y;Sun Y;Han L
TRIM 50属于TRIM蛋白家族，与多种癌症的发病机制有关。然而，TRIM 50在肝细胞癌（HCC）中的作用仍有待阐明。在此，我们发现TRIM 50在肝癌组织中的表达与相应的非癌肝组织相比显著降低，并且其表达降低与晚期疾病进展显著相关。通过外源性过表达TRIM 50的HCC细胞功能获得实验显示，HCC细胞的增殖、集落形成、迁移和侵袭能力均受到显著抑制，而通过TRIM 50敲低的HCC细胞功能丧失实验显示，HCC细胞的这些恶性行为均显著增加。进一步的研究表明TRIM 50可以直接与SNAIL结合，并诱导K-48连接的SNAIL蛋白的多处降解，从而进一步逆转SNAIL介导的肝癌细胞上皮间质转化（EMT）过程。通过异种移植瘤模型的体内测定验证了TRIM 50对HCC的抗肿瘤作用。总之，这些结果表明TRIM 50通过直接靶向SNAIL和逆转EMT而在HCC细胞中起肿瘤抑制剂的作用，这进一步表明TRIM 50的正调控可能是SNAIL过表达的HCC细胞的新的治疗策略。
Tripartite motif-containing 50 (TRIM50) belongs to the tripartite motif (TRIM) protein family, which has been implicated in the pathogenesis of multiple cancers. However, the role of TRIM50 in hepatocellular carcinoma (HCC) remains to be clarified. Here we showed that TRIM50 expression was significantly decreased in liver cancer tissues compared with corresponding non-cancerous liver tissues, and its decreased expression was significantly correlated with advanced disease progression. Gain-of-function assay by exogenous overexpression of TRIM50 in HCC cells showed that proliferation, colony formation, migration and invasion of HCC cells were significantly inhibited, whereas loss-of-function assay by TRIM50 knockdown showed that these malignant behaviors of HCC cells were significantly increased. Further investigation showed that TRIM50 could directly bind with SNAIL and induced K-48 linked poly-ubiquitous degradation of SNAIL protein, which further reversed SNAIL-mediated epithelial-to-mesenchymal transition (EMT) process of HCC cells. In vivo assay by xenograft tumor model verified the antitumor effect of TRIM50 on HCC. Taken together, these results showed that TRIM50 acted as a tumor suppressor in HCC cells by directly targeting SNAIL and reversing EMT, which further indicated that positive modulation of TRIM50 might be a novel therapeutic strategy for SNAIL overexpressed HCC cells.
登录
查看更多内容
影响因子：
25.7
作者：
Jiang S;Minter LC;Stratton SA;Yang P;Abbas HA;Akdemir ZC;Pant V;Post S;Gagea M;Lee RG;Lozano G;Barton MC
通讯作者：
Barton MC
DOI：
10.1073/pnas.1710799114
发表时间：
2017-09-26
影响因子：
11.1
作者：
Oberstein, Adam;Shenk, Thomas
通讯作者：
Shenk, Thomas
高剂量细胞外 ATP 将贴壁依赖性和贴壁非依赖性肝癌细胞的自噬转变为凋亡
影响因子：
3.5
作者：
Wei, Qing;Zhang, Ying;Han, Lihui
通讯作者：
Han, Lihui
BEL7402 肝癌细胞获得失巢凋亡抗性揭示了类似 Synoikis 的生存方式
影响因子：
9.7
作者：
Zhang, Zhiyong;Cao, Lill;Sun, Wensheng
通讯作者：
Sun, Wensheng
雌激素通过 ER beta 介导的 NLRP3 炎症小体上调抑制肝细胞癌细胞
影响因子：
5
作者：
Wei, Qing;Guo, Pengbo;Han, Lihui
通讯作者：
Han, Lihui