Upregulation of OGT by Caveolin-1 promotes hepatocellular carcinoma cell migration and invasion.


Journal

Cell biology international
ISSN: 1095-8355
Titre abrégé: Cell Biol Int
Pays: England
ID NLM: 9307129

Informations de publication

Date de publication:
Nov 2021
Historique:
revised: 26 05 2021
received: 07 12 2020
accepted: 03 07 2021
pubmed: 22 7 2021
medline: 17 2 2022
entrez: 21 7 2021
Statut: ppublish

Résumé

Caveolin-1 (CAV1), a major structural protein of caveolae, is reported to exert a positive regulatory effect on tumor growth and to play a crucial role in hepatocellular carcinoma (HCC) cell metastasis by regulating glycosyltransferase expression and cellular glycosylation. However, the role of CAV1 in modulating protein glycosylation and tumor metastasis remains to be further elucidated. In the present study, we showed that CAV1 promoted the expression of O-GlcNAc transferase (OGT), which catalyzed the addition of O-GlcNAc residues to a variety of nuclear and cytoplasmic proteins. In human HCC cell lines with different metastatic potentials, high levels of OGT and cellular O-GlcNAcylation were associated with CAV1 expression and cell metastasis. Overexpression of CAV1 increased the levels of OGT and O-GlcNAcylation, and cell migration was also increased. Furthermore, CAV1 was found to reduce the expression of Runt-related transcription factor 2 (RUNX2) in HCC cells. Subsequently, this effect resulted in the attenuation of the RUNX2-induced transcription of microRNA24 (miR24), a microRNA previously shown to suppress OGT mRNA expression by targeting its 3' untranslated regions (UTR). Finally, we demonstrated that CAV1 induced cellular O-GlcNAcylation and HCC cell invasion. This study provides evidence of CAV1-mediated increases in OGT expression and O-GlcNAcylation. These data provide insight into a novel mechanism underlying HCC metastasis and suggest a novel strategy for the treatment of HCC.

Identifiants

pubmed: 34288245
doi: 10.1002/cbin.11673
doi:

Substances chimiques

CAV1 protein, human 0
Caveolin 1 0
Core Binding Factor Alpha 1 Subunit 0
MIRN24 microRNA, human 0
MicroRNAs 0
RUNX2 protein, human 0
N-Acetylglucosaminyltransferases EC 2.4.1.-
O-GlcNAc transferase EC 2.4.1.-
OGT protein, human EC 2.4.1.255

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2251-2263

Subventions

Organisme : Fundamental Research Funds for the Central Universities
ID : DUT20YG116
Organisme : Fundamental Research Funds for the Central Universities
ID : DUT20YG130
Organisme : Natural Science Foundation of Liaoning Province
ID : 2019-MS-042
Organisme : National Science and Technology Major Project of China
ID : 2018ZX10302205
Organisme : Natural Science Foundation of China
ID : 31870793
Organisme : Natural Science Foundation of China
ID : 31971214

Informations de copyright

© 2021 International Federation for Cell Biology.

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Auteurs

Lingyan Wang (L)

Department of Biochemistry, School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Yuan Feng (Y)

Department of Biochemistry, School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Cheng Zhang (C)

Department of Biochemistry, School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Xixi Chen (X)

Department of Biochemistry, School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Huang Huang (H)

Department of Biochemistry, School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Wenli Li (W)

Department of Biochemistry, School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Jianing Zhang (J)

Department of Biochemistry, School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Yubo Liu (Y)

Department of Biochemistry, School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

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