論文 - 詳細
RRC ID | 63003 |
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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 |