PMID- 37251542
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230531
IS  - 2391-5463 (Print)
IS  - 2391-5463 (Electronic)
VI  - 18
IP  - 1
DP  - 2023
TI  - Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates 
      hepatocellular carcinoma cell chemotaxis and metastasis.
PG  - 20230708
LID - 10.1515/med-2023-0708 [doi]
LID - 20230708
AB  - 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.
CI  - (c) 2023 the author(s), published by De Gruyter.
FAU - Yang, Gangqi
AU  - Yang G
AD  - Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical 
      University, Guiyang, Guizhou 550001, China.
AD  - General Surgery Department and Neurology Department, Xuanwu Hospital, National 
      Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
AD  - Guangdong Key Laboratory of Epigenetics, College of Life Sciences and 
      Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, China.
AD  - Comprehensive Liver Cancer Center, 5th Medical Center of the PLA General 
      Hospital, Beijing 100039, China.
FAU - Li, Hongyan
AU  - Li H
AD  - General Surgery Department and Neurology Department, Xuanwu Hospital, National 
      Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
FAU - Dong, Zheng
AU  - Dong Z
AD  - Comprehensive Liver Cancer Center, 5th Medical Center of the PLA General 
      Hospital, Beijing 100039, China.
FAU - Deng, Kai
AU  - Deng K
AD  - The First Affiliated Hospital of Chongqing Medical College, Chongqing 400016, 
      China.
FAU - Lu, Yinying
AU  - Lu Y
AD  - Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical 
      University, Guiyang, Guizhou 550001, China.
AD  - Comprehensive Liver Cancer Center, 5th Medical Center of the PLA General 
      Hospital, Beijing 100039, China.
AD  - Guangdong Key Laboratory of Epigenetics, College of Life Sciences and 
      Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, China.
LA  - eng
PT  - Journal Article
DEP - 20230525
PL  - Poland
TA  - Open Med (Wars)
JT  - Open medicine (Warsaw, Poland)
JID - 101672167
PMC - PMC10224614
OTO - NOTNLM
OT  - DMF
OT  - ELMO1
OT  - NPM1
OT  - chemotaxis
OT  - hepatocellular carcinoma
OT  - metastasis
COIS- Conflict of interest: The authors have no conflict of interest to declare.
EDAT- 2023/05/30 13:07
MHDA- 2023/05/30 13:08
PMCR- 2023/05/25
CRDT- 2023/05/30 11:40
PHST- 2022/08/18 00:00 [received]
PHST- 2023/03/24 00:00 [revised]
PHST- 2023/04/17 00:00 [accepted]
PHST- 2023/05/30 13:08 [medline]
PHST- 2023/05/30 13:07 [pubmed]
PHST- 2023/05/30 11:40 [entrez]
PHST- 2023/05/25 00:00 [pmc-release]
AID - med-2023-0708 [pii]
AID - 10.1515/med-2023-0708 [doi]
PST - epublish
SO  - Open Med (Wars). 2023 May 25;18(1):20230708. doi: 10.1515/med-2023-0708. 
      eCollection 2023.