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

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.

• Authors: Mengjia Song, Qiuzhong Pan, Jieying Yang, Junyi He, Jianxiong Zeng, Shaoyan Cheng, Yue Huang, Zi-Qi Zhou, Qian Zhu, Chaopin Yang, Yulong Han, Yan Tang, Hao Chen, De-Sheng Weng, Jian-Chuan Xia
• Journal: British journal of cancer (Br J Cancer) Vol. 123 Issue 10 Pg. 1521-1534 (11 2020) ISSN: 1532-1827 [Electronic] England
• PMID: 32801345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Galectin 3
• beta Catenin

Topics

• Animals
• Carcinogenesis (genetics, metabolism)
• Carcinoma, Hepatocellular (genetics, metabolism, mortality, pathology)
• Cell Adhesion (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Galectin 3 (physiology)
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (genetics, metabolism, mortality, pathology)
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Metastasis
• Neoplasms, Vascular Tissue (genetics, mortality, secondary)
• Survival Analysis
• Tissue Array Analysis
• Wnt Signaling Pathway (genetics)
• beta Catenin (genetics, metabolism)