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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. [ABSTRACT FROM AUTHOR]

Please find the correct Figure S5a here: GLO:I6Z7/18aug21:advs2922-fig-0001.jpg PHOTO (COLOR): S5 RNF219-mediated -catenin reduction activates Wnt/ -catenin and YAP1 pathways. B 2021 b , I 8 i , 2001961 DOI: 10.1002/advs.202001961 In the originally published article, the wrong western blotting image of loading control I i -actin was mistakenly used in the upper right panel in HCCLM3-BM4 cells in Figure S5A (Supporting Information). RNF219/ -Catenin/LGALS3 Axis Promotes Hepatocellular Carcinoma Bone Metastasis and Associated Skeletal Complications. [Extracted from the article]