RRC ID 63003
著者 Song M, Pan Q, Yang J, He J, Zeng J, Cheng S, Huang Y, Zhou ZQ, Zhu Q, Yang C, Han Y, Tang Y, Chen H, Weng DS, Xia JC.
タイトル Galectin-3 favours tumour metastasis via the activation of β-catenin signalling in hepatocellular carcinoma.
ジャーナル Br J Cancer
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.
巻・号 123(10)
ページ 1521-1534
公開日 2020-11-1
DOI 10.1038/s41416-020-1022-4
PII 10.1038/s41416-020-1022-4
PMID 32801345
PMC PMC7653936
MeSH Animals Carcinogenesis / genetics Carcinogenesis / metabolism Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / mortality Carcinoma, Hepatocellular / 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 Liver Neoplasms / metabolism Liver Neoplasms / mortality Liver Neoplasms / pathology* Mice, Inbred BALB C Mice, Nude Neoplasm Metastasis Neoplasms, Vascular Tissue / genetics Neoplasms, Vascular Tissue / mortality Neoplasms, Vascular Tissue / secondary Survival Analysis Tissue Array Analysis Wnt Signaling Pathway / genetics beta Catenin / genetics* beta Catenin / metabolism
IF 5.791
リソース情報
ヒト・動物細胞 HuH-7