Targeting anillin inhibits tumorigenesis and tumor growth in hepatocellular carcinoma via impairing cytokinesis fidelity.
Animals
Carcinoma, Hepatocellular
/ pathology
Cell Line, Tumor
Cell Proliferation
/ genetics
Cell Transformation, Neoplastic
/ genetics
Contractile Proteins
Cytokinesis
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms
/ pathology
Mice
Microfilament Proteins
/ metabolism
Polyploidy
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
17
10
2021
accepted:
08
03
2022
revised:
21
02
2022
pubmed:
29
4
2022
medline:
31
5
2022
entrez:
28
4
2022
Statut:
ppublish
Résumé
Targeting cytokinesis can suppress tumor growth by blocking cell division and promoting apoptosis. We aimed to characterize key cytokinesis regulator in hepatocellular carcinoma (HCC) progression, providing insights into identifying promising HCC therapeutic targets. The unbiased bioinformatic screening identified Anillin actin binding protein (ANLN) as a critical cytokinesis regulator involved in HCC development. Functional assay demonstrated that knockdown of ANLN inhibited HCC growth by inducing cytokinesis failure and DNA damage, leading to multinucleation and mitotic catastrophe. Mechanistically, ANLN acts as a scaffold to strengthen interaction between RACGAP1 and PLK1. ANLN promotes PLK1-mediated RACGAP1 phosphorylation and RhoA activation to ensure cytokinesis fidelity. To explore the function of ANLN in HCC tumorigenesis, we hydrodynamically transfected c-Myc and NRAS plasmids into Anln
Identifiants
pubmed: 35477750
doi: 10.1038/s41388-022-02274-1
pii: 10.1038/s41388-022-02274-1
doi:
Substances chimiques
Contractile Proteins
0
Microfilament Proteins
0
anillin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3118-3130Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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