Open AccessSlug promoted vasculogenic mimicry in hepatocellular carcinoma
Author(s) -
Sun Dan,
Sun Baocun,
Liu Tieju,
Zhao Xiulan,
Che Na,
Gu Qiang,
Dong Xueyi,
Yao Zhi,
Li Rui,
Li Jing,
Chi Jiadong,
Sun Ran
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12087
Subject(s) - slug , vasculogenic mimicry , epithelial–mesenchymal transition , metastasis , cancer research , angiogenesis , biology , hepatocellular carcinoma , cancer stem cell , cancer , pathology , microbiology and biotechnology , stem cell , medicine , genetics
Abstract Vasculogenic mimicry ( VM ) refers to the unique capability of aggressive tumour cells to mimic the pattern of embryonic vasculogenic networks. Epithelial–mesenchymal transition ( EMT ) regulator slug have been implicated in the tumour invasion and metastasis of human hepatocellular carcinoma ( HCC ). However, the relationship between slug and VM formation is not clear. In the study, we demonstrated that slug expression was associated with EMT and cancer stem cell (CSCs) phenotype in HCC patients. Importantly, slug showed statistically correlation with VM formation. We consistently demonstrated that an overexpression of slug in HCC cells significantly increased CSC s subpopulation that was obvious by the increased clone forming efficiency in soft agar and by flowcytometry analysis. Meantime, the VM formation and VM mediator overexpression were also induced by slug induction. Finally, slug overexpression lead to the maintenance of CSC s phenotype and VM formation was demonstrated in vivo . Therefore, the results of this study indicate that slug induced the increase and maintenance of CSC s subpopulation and contributed to VM formation eventually. The related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis.