Galectin-3 favours tumour metastasis via the activation of β-catenin signalling in hepatocellular carcinoma

Author:

Song Mengjia,Pan Qiuzhong,Yang Jieying,He Junyi,Zeng Jianxiong,Cheng Shaoyan,Huang Yue,Zhou Zi-Qi,Zhu Qian,Yang Chaopin,Han Yulong,Tang Yan,Chen Hao,Weng De-Sheng,Xia Jian-ChuanORCID

Abstract

Abstract Background High probability of metastasis limited the long-term survival of patients with hepatocellular carcinoma (HCC). Our previous study revealed that Galectin-3 was closely associated with poor prognosis in HCC patients. Methods The effects of Galectin-3 on tumour metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated. Results Galectin-3 showed a close correlation with vascular invasion and poor survival in a large-scale study in HCC patients from multiple sets. Galectin-3 was significantly involved in diverse metastasis-related processes in HCC cells, such as angiogenesis and epithelial-to-mesenchymal transition (EMT). Mechanistically, Galectin-3 activated the PI3K-Akt-GSK-3β-β-catenin signalling cascade; the β-catenin/TCF4 transcriptional complex directly targeted IGFBP3 and vimentin to regulate angiogenesis and EMT, respectively. In animal models, Galectin-3 enhanced the tumorigenesis and metastasis of HCC cells via β-catenin signalling. Moreover, molecular deletion of Galectin-3-β-catenin signalling synergistically improved the antitumour effect of sorafenib. Conclusions The Galectin-3-β-catenin-IGFBP3/vimentin signalling cascade was determined as a central mechanism controlling HCC metastasis, providing possible biomarkers for predicating vascular metastasis and sorafenib resistance, as well as potential therapeutic targets for the treatment of HCC patients.

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Oncology

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