RNF219/ α ‐Catenin/LGALS3 Axis Promotes Hepatocellular Carcinoma Bone Metastasis and Associated Skeletal Complications

RNF219/ α ‐Catenin/LGALS3 Axis Promotes Hepatocellular Carcinoma Bone Metastasis and Associated Skeletal Complications.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1002/advs.202001961
Journal or Publication Title: Advanced Science
Volume: 8
Number: 4
Page Range: p. 2001961
Date: 2021
Divisions: Lipid Cell Biology
Depositing User: General Admin
Identification Number: 10.1002/advs.202001961
ISSN: 2198-3844
Date Deposited: 29 Mar 2021 05:54
Abstract:

The incidence of bone metastases in hepatocellular carcinoma (HCC) has increased prominently over the past decade owing to the prolonged overall survival of HCC patients. However, the mechanisms underlying HCC bone-metastasis remain largely unknown. In the current study, HCC-secreted lectin galactoside-binding soluble 3 (LGALS3) is found to be significantly upregulated and correlates with shorter bone-metastasis-free survival of HCC patients. Overexpression of LGALS3 enhances the metastatic capability of HCC cells to bone and induces skeletal-related events by forming a bone pre-metastatic niche via promoting osteoclast fusion and podosome formation. Mechanically, ubiquitin ligaseRNF219-meidated α-catenin degradation prompts YAP1/β-catenin complex-dependent epigenetic modifications of LGALS3 promoter, resulting in LGALS3 upregulation and metastatic bone diseases. Importantly, treatment with verteporfin, a clinical drug for macular degeneration, decreases LGALS3 expression and effectively inhibits skeletal complications of HCC. These findings unveil a plausible role for HCC-secreted LGALS3 in pre-metastatic niche and can suggest a promising strategy for clinical intervention in HCC bone-metastasis.

© 2020 The Authors. Published by Wiley‐VCH GmbH.

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Zhang, Shuxia
UNSPECIFIED
Xu, Yingru
UNSPECIFIED
Xie, Chan
UNSPECIFIED
Ren, Liangliang
UNSPECIFIED
Wu, Geyan
UNSPECIFIED
Yang, Meisongzhu
UNSPECIFIED
Wu, Xingui
UNSPECIFIED
Tang, Miaoling
UNSPECIFIED
Hu, Yameng
UNSPECIFIED
Li, Ziwen
UNSPECIFIED
Yu, Ruyuan
UNSPECIFIED
Liao, Xinyi
UNSPECIFIED
Mo, Shuang
UNSPECIFIED
Wu, Jueheng
UNSPECIFIED
Li, Mengfeng
UNSPECIFIED
Song, Erwei
UNSPECIFIED
Qi, Yanfei
UNSPECIFIED
Song, Libing
UNSPECIFIED
Li, Jun
UNSPECIFIED
Last Modified: 08 Apr 2021 05:20
URI: https://eprints.centenary.org.au/id/eprint/948

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