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Protease-activated receptor-1 (PAR1) promotes epithelial-endothelial transition through Twist1 in hepatocellular carcinoma.

Authors :
Xiao T
Zhang Q
Zong S
Zhong WL
Qin Y
Bi Z
Chen S
Liu HJ
Wei JJ
Zhou BJ
Wang LM
Zhou HG
Liu YR
Sun T
Yang C
Source :
Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2018 Aug 06; Vol. 37 (1), pp. 185. Date of Electronic Publication: 2018 Aug 06.
Publication Year :
2018

Abstract

Background: Tumor cells transfer into endothelial cells by epithelial-endothelial transition (EET), which is characterized by vasculagenic mimicry (VM) in morphology. VM can change tumor microcirculation, progression, and metastasis. However, the molecular mechanisms of endothelial-like transition remain unclear. EET is a subtype of epithelial-mesenchymal transition (EMT). Twist1, a transcriptional regulatory factor of EMT, is an important factor that induces EET in hepatocellular carcinoma(HCC), but the upstream signal of Twist1 is unclear.<br />Methods: Expression plasmids, Ca mobilization, and three-dimensional cultures were evaluated. Western blot assay, reporter gene assay, and immunofluorescence staining were conducted. A murine xenograft model was established. Analyses of immunohistochemistry, patient samples, and complementary DNA (cDNA) microarrays were also performed.<br />Results: This study demonstrated that protease-activated receptor-1 (PAR1) can increase the expression of endothelial markers and enhance VM formation by upregulating Twist1 both in vitro and in vivo through thrombin binding. Thrombin not only activates PAR1 but also promotes PAR1 internalization in a time-dependent manner. Clinical pathological analysis further confirms that PAR1 expression is directly correlated with the endothelial marker expression, VM formation, and metastasis and indicates poor survival rate of patients with tumors.<br />Conclusion: PAR1 promotes EET through Twist1 in HCC.

Details

Language :
English
ISSN :
1756-9966
Volume :
37
Issue :
1
Database :
MEDLINE
Journal :
Journal of experimental & clinical cancer research : CR
Publication Type :
Academic Journal
Accession number :
30081924
Full Text :
https://doi.org/10.1186/s13046-018-0858-4