O-GlcNAcylation on Rab3A attenuates its effects on mitochondrial oxidative phosphorylation and metastasis in hepatocellular carcinoma.
O-GlcNAcylation on Rab3A attenuates its effects on mitochondrial oxidative phosphorylation and metastasis in hepatocellular carcinoma.
复制标题
Rab3A 上的 O-GlcNAc 酰化减弱了其对肝细胞癌线粒体氧化磷酸化和转移的影响
DOI：
10.1038/s41419-018-0961-7
复制
发表时间：
2018-09-20
影响因子：
9
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Wu W;Zheng X;Wang J;Yang T;Dai W;Song S;Fang L;Wang Y;Gu J
Rab3A是一种小的ras样GTPase，对膜交通至关重要。虽然Rab3A在几种癌症中的功能已被报道，但Rab3A在肝细胞癌（HCC）中的作用尚未确定。为了研究Rab3A在HCC进展中的潜在作用，我们首先测定了HCC组织中Rab3A的水平，发现在大多数肿瘤组织中Rab3A的mRNA和蛋白水平上调。然而，体外数据显示，在大多数HCC细胞系中，降低Rab3A并没有显著的影响，在PLC/PRF/5细胞中过表达Rab3A甚至会抑制迁移和侵袭。同时，Rab3A在HCC患者中的表达上调与HCC患者的转移及总生存率无相关性。这些相互矛盾的数据表明Rab3A可能作为转移抑制因子，其作用在大多数HCC细胞中可能减弱。进一步的实验发现，o - glcnac酰化作用通过调节Rab3A的gtp结合活性，是减弱Rab3A介导作用的关键，并在体外和体内验证了Rab3A及其异常to - glcnac酰化对HCC转移的影响。我们还发现Rab3A和itso - glcnac酰化在线粒体氧化磷酸化（mtOXPHOS）中具有相反的作用，它们在HCC转移中的功能部分取决于它们对代谢重编程的影响。
Rab3A is a small Ras-like GTPase critical for membrane traffic. Although the functions of Rab3A have been reported in several cancers, the roles of Rab3A in hepatocellular carcinoma (HCC) have never been determined. To investigate the potential roles of Rab3A in HCC progression, we first determined Rab3A levels in HCC tissues and observed upregulated mRNA and protein levels of Rab3A in most tumor tissues. However, in vitro data showed that decreasing Rab3A in most HCC cell lines conferred no significant effects and overexpressing Rab3A in PLC/PRF/5 cells even inhibited migration and invasion. Meanwhile, the upregulation of Rab3A in HCC patients did not correlate with metastasis or overall survival of HCC patients. These contradict data suggested that Rab3A might act as metastatic suppressor and its effects might be attenuated in most HCC cells. Further experiments revealed thatO-GlcNAcylation on Rab3A was key for attenuating Rab3A-mediated effects by regulating its GTP-binding activity, and verified the effects of Rab3A and its aberrantO-GlcNAcylation on HCC metastasis in vitro and in vivo. We also found that Rab3A and itsO-GlcNAcylation had opposite roles in mitochondria oxidative phosphorylation (mtOXPHOS), and their functions on HCC metastasis were partially depended on their effects on metabolic reprogramming.
登录
查看更多内容
影响因子：
15.8
作者：
Kim JH;Sohn BH;Lee HS;Kim SB;Yoo JE;Park YY;Jeong W;Lee SS;Park ES;Kaseb A;Kim BH;Kim WB;Yeon JE;Byun KS;Chu IS;Kim SS;Wang XW;Thorgeirsson SS;Luk JM;Kang KJ;Heo J;Park YN;Lee JS
通讯作者：
Lee JS
影响因子：
5.3
作者：
Eriksson, Matilda;Ambroise, Gorbatchev;Vakifahmetoglu-Norberg, Helin
通讯作者：
Vakifahmetoglu-Norberg, Helin
DOI：
10.1034/j.1600-0749.2000.130505.x
发表时间：
2000-10-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Araki, K;Horikawa, T;Ichihashi, M
通讯作者：
Ichihashi, M
影响因子：
16
作者：
Ferrer, Christina M.;Lynch, Thomas P.;Sodi, Valerie L.;Falcone, John N.;Schwab, Luciana P.;Peacock, Danielle L.;Vocadlo, David J.;Seagroves, Tiffany N.;Reginato, Mauricio J.
通讯作者：
Reginato, Mauricio J.
影响因子：
9.7
作者：
Lu, Jianrong;Tan, Ming;Cai, Qingsong
通讯作者：
Cai, Qingsong