CHIP-mediated CIB1 ubiquitination regulated epithelial-mesenchymal transition and tumor metastasis in lung adenocarcinoma.
CHIP-mediated CIB1 ubiquitination regulated epithelial-mesenchymal transition and tumor metastasis in lung adenocarcinoma.
复制标题
CHIP介导的CIB1泛素化调控肺腺癌上皮间质转化和肿瘤转移
DOI：
10.1038/s41418-020-00635-5
复制
发表时间：
2021-03
影响因子：
12.4
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Liu Y;Zhou Y;Zhang P;Li X;Duan C;Zhang C
CIB 1是调节细胞粘附、迁移和分化的钙调蛋白的同系物。它被认为是许多肿瘤细胞中的癌基因;然而，它在肺腺癌（LAC）中的作用尚未研究。本研究采用免疫组化方法检测CIB 1在LAC组织及癌旁正常组织中的表达水平，并分析CIB 1表达与患者临床病理特征的关系。在体外和体内测定CIB 1对LAC细胞的上皮-间质转化（EMT）、迁移和转移的影响。使用电喷雾质谱法（LS-MS）鉴定与CIB 1相互作用的蛋白质，并在以下测定中选择CHIP。热休克蛋白70相互作用蛋白（CHIP）是一种泛素E3连接酶。我们发现CHIP可以通过促进CIB 1的多聚泛素化及其随后的蛋白酶体降解来降解CIB 1。此外，CIB 1的赖氨酸残基10和65是CIB 1的泛素化位点。此外，CHIP介导的CIB 1下调对于抑制LAC的转移和迁移至关重要。这些结果表明，CHIP介导的CIB 1泛素化可以调节上皮间质和肿瘤转移在LAC中。
CIB1 is a homolog of calmodulin that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in many tumor cells; however, its role in lung adenocarcinoma (LAC) has not been studied. In this study, the expression levels of CIB1 in LAC tissues and adjacent normal tissues were examined by immunohistochemistry, and the relationship between CIB1 expression and patient clinicopathological characteristics was analyzed. The effects of CIB1 on epithelial–mesenchymal transition (EMT), migration, and metastasis of LAC cells were determined in vitro and vivo. Proteins interacting with CIB1 were identified using electrospray mass spectrometry (LS-MS), and CHIP was selected in the following assays. Carboxyl-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin E3 ligase. We show that CHIP can degrade CIB1 via promoting polyubiquitination of CIB1 and its subsequent proteasomal degradation. Besides, lysine residue 10 and 65 of CIB1 is the ubiquitinated site of CIB1. Furthermore, CHIP-mediated CIB1 downregulation is critical for the suppression of metastasis and migration of LAC. These results indicated that CHIP-mediated CIB1 ubiquitination could regulate epithelial–mesenchymal and tumor metastasis in LAC.
登录
查看更多内容
影响因子：
8
作者：
Eberlein, C.;Rooney, C.;Barry, S. T.
通讯作者：
Barry, S. T.
影响因子：
3.8
作者：
Black JL;Harrell JC;Leisner TM;Fellmeth MJ;George SD;Reinhold D;Baker NM;Jones CD;Der CJ;Perou CM;Parise LV
通讯作者：
Parise LV
影响因子：
37.3
作者：
Dong S;Zhao J;Wei J;Bowser RK;Khoo A;Liu Z;Luketich JD;Pennathur A;Ma H;Zhao Y
通讯作者：
Zhao Y
影响因子：
11.5
作者：
Cheng, Ai-Lan;Huang, Wei-Guo;Xiao, Zhi-Qiang
通讯作者：
Xiao, Zhi-Qiang
影响因子：
11.2
作者：
Luan H;Mohapatra B;Bielecki TA;Mushtaq I;Mirza S;Jennings TA;Clubb RJ;An W;Ahmed D;El-Ansari R;Storck MD;Mishra NK;Guda C;Sheinin YM;Meza JL;Raja S;Rakha EA;Band V;Band H
通讯作者：
Band H