Back to Search Start Over

CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma

CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma

Authors :
Shi-Jie Wang
Dong Chao
Wei Wei
Gang Nan
Jia-Yue Li
Fen-Ling Liu
Ling Li
Jian-Li Jiang
Hong-Yong Cui
Zhi-Nan Chen
Source :
Journal of Experimental & Clinical Cancer Research, Vol 39, Iss 1, Pp 1-18 (2020)
Publication Year :
2020
Publisher :
BMC, 2020.

Abstract

Abstract Background Mounting evidence suggests that solid tumors display the features of collective invasion, however, the molecular mechanisms are far from clear. This study aims to verify the role and the underlying mechanisms of CD147 in collective invasion in hepatocellular carcinoma. Methods Immunostaining was used to analyze human hepatocellular carcinoma specimens and three-dimensional cultures. Three-dimensional invasion model was established to mimic in vivo invasion. RNA-sequencing was used to identify downstream effectors. Results Human hepatocellular carcinoma underwent collective invasion and CD147 was observed to be upregulated at the invasive front of tumor cell groups. CD147 was demonstrated to promote collective invasion using the modified three-dimensional invasion model, which recapitulated the main features of collective invasion. Through transcriptome analysis and enzyme activity assay, we found that CD147 enhanced cathepsin B expression and activity. Upregulated cathepsin B in hepatocellular carcinoma cells facilitated migration and invasion, which mediated CD147-induced invasive phenotype in hepatocellular carcinoma. In terms of mechanism, we found that CD147 promoted cathepsin B transcription by activating β-catenin signaling as a result of reduced GSK-3β expression. Furthermore, we found that elevated expression of CD147 as well as cathepsin B were correlated with poor prognosis in patients with hepatocellular carcinoma. Conclusions CD147 promotes hepatocellular carcinoma cells collective invasion via upregulating cathepsin B expression and targeting CD147 would be valuable for the development of novel therapeutic modalities against invasion and metastasis of cancer.

Details

Language :
English
ISSN :
17569966
Volume :
39
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Experimental & Clinical Cancer Research
Publication Type :
Academic Journal
Accession number :
edsdoj.9e858b5f1e64731a944b2f5e8ad8be3
Document Type :
article
Full Text :
https://doi.org/10.1186/s13046-020-01647-2