Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis

作者全名："Yang, Gangqi; Li, Hongyan; Dong, Zheng; Deng, Kai; Lu, Yinying"

作者地址："[Yang, Gangqi; Lu, Yinying] Guizhou Med Univ, Affiliated Hosp, Dept Infect Dis, Guiyang 550001, Guizhou, Peoples R China; [Yang, Gangqi; Dong, Zheng; Lu, Yinying] 5th Med Ctr PLA Gen Hosp, Comprehens Liver Canc Ctr, Beijing 100039, Peoples R China; [Yang, Gangqi; Lu, Yinying] Shenzhen Univ, Coll Life Sci & Oceanog, Guangdong Key Lab Epigenet, Shenzhen 518055, Guangdong, Peoples R China; [Yang, Gangqi; Li, Hongyan] Xuanwu Hosp, Natl Clin Res Ctr Geriatr Dis, Gen Surg Dept, Neurol Dept, Beijing 100053, Peoples R China; [Deng, Kai] First Affiliated Hosp, Chongqing Med Coll, Chongqing 400016, Peoples R China"

通信作者："Lu, YY (通讯作者)，Guizhou Med Univ, Affiliated Hosp, Dept Infect Dis, Guiyang 550001, Guizhou, Peoples R China.; Lu, YY (通讯作者)，5th Med Ctr PLA Gen Hosp, Comprehens Liver Canc Ctr, Beijing 100039, Peoples R China.; Lu, YY (通讯作者)，Shenzhen Univ, Coll Life Sci & Oceanog, Guangdong Key Lab Epigenet, Shenzhen 518055, Guangdong, Peoples R China.; Li, HY (通讯作者)，Xuanwu Hosp, Natl Clin Res Ctr Geriatr Dis, Gen Surg Dept, Neurol Dept, Beijing 100053, Peoples R China."

来源：OPEN MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000994480200001

JCR分区：Q2

影响因子：1.7

年份：2023

卷号：18

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：NPM1; ELMO1; chemotaxis; metastasis; hepatocellular carcinoma; DMF

摘要："The chemokine, C-X-C motif chemokine ligand 12 (CXCL12) and its G-protein-coupled receptor (GPCR) and C-X-C chemokine receptor type 4 (CXCR4), are closely associated with promoting hepatocellular carcinoma (HCC) chemotaxis and metastasis. The binding of CXCL12 and CXCR4 depends on the heterotrimeric Gi proteins to regulate actin polymerisation and mobility in HCC. Although the role of GPCR/Gi signalling in carcinogenesis migration has been intensively studied, the detailed mechanism remains largely unknown. In this study, a small interfering RNA technique was used to knock down the Nucleophosmin 1 (NPM1) gene expression. Through the chemotaxis and invasion assays, wound healing, proliferation, filamentous-actin, immunofluorescence, immunohistochemical assays, and co-immunoprecipitation assays, we investigated the specific biological role and underlying mechanisms of the NPM1 in HCC. Additionally, dimethyl fumarate (DMF), a fumaric acid ester, was used to inhibit the HCC cell chemokines and metastasis by regulating ELMO1 and NPM1. Therefore, this study reported that NPM1 gene expression was upregulated in the HCC tissues and cell lines. The NPM1 knockdown significantly inhibited the proliferation, migration, and chemotaxis of the HepG2 cells in vitro. Further mechanistic studies suggested that the NPM1 interacts with ELMO1 and the CXCL12/CXCR4 pathway activates NPM1-dependent regulation of the ELMO1 localisation. Furthermore, the DMF significantly inhibited tumour metastasis induced by the NPM1/ELMO1 signalling pathway, as observed in in vitro cell functional experiments. These data suggested that as a potentially novel therapeutic approach, the simultaneous targeting of NPM1 and ELMO1 could effectively be used to treat HCC."

基金机构："National Natural Science Foundation of China [81902495]; Natural Science Foundation of Beijing Municipality [7212099]; R&D Program of Beijing Municipal Education Commission [KM202110025019]; National Natural Science Foundation of China [82271373]; Beijing Natural Science Foundation [7232075]; China Postdoctoral Science Foundation [2021M702463]; Science, Technology, and Innovation Commission of Shenzhen Municipality [KCX-FZ202002011006448]"

基金资助正文："This study was supported by grants from National Natural Science Foundation of China (81902495), Natural Science Foundation of Beijing Municipality (7212099), R&D Program of Beijing Municipal Education Commission (KM202110025019), National Natural Science Foundation of China (82271373), Beijing Natural Science Foundation (7232075), China Postdoctoral Science Foundation (2021M702463), Science, Technology, and Innovation Commission of Shenzhen Municipality (KCX-FZ202002011006448)."