Galectin-3 Favours Tumour Metastasis Via the Activation of β-catenin Signalling in Hepatocellular Carcinoma

Overview

Journal Br J Cancer

Specialty Oncology

Date 2020 Aug 18

PMID 32801345

Citations 38

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

Affiliations

Soon will be listed here.

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.

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