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

• DOI: 10.1002/advs.202001961
• Publication Date: 2020-12-31T10:57:21Z
• Authors: Shuxia Zhang; Yingru Xu; Chan Xie; Liangliang Ren; Geyan Wu; Meisongzhu Yang; Xingui Wu; Miaoling Tang; Yameng Hu; Ziwen Li; Ruyuan Yu; Xinyi Liao; Shuang Mo; Jueheng Wu; Mengfeng Li; Erwei Song; Yanfei Qi; Libing Song; Jun Li
• Keywords: 0301 basic medicine; LGALS3; 0303 health sciences; Science; Q; Correction; RNF219; hepatocellular carcinoma; Full Papers; 03 medical and health sciences; skeletal‐related events; bone metastasis

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