University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Factor VII promotes hepatocellular carcinoma progression through ERK-TSC signaling

McVey, JH, Tsai, M-C, Chen, K-D and Wang, C-C (2016) Factor VII promotes hepatocellular carcinoma progression through ERK-TSC signaling CELL DEATH DISCOVERY, 1.

CDDiscovery_chen_2015.pdf - Accepted version Manuscript
Available under License : See the attached licence file.

Download (1MB) | Preview
Text (licence)
Available under License : See the attached licence file.

Download (33kB) | Preview


We previously demonstrated PAR2 starts upstreamed with tissue factor (TF) and factor VII (FVII), inhibited autophagy via mTOR signaling in HCC. However, the mechanism underlying for merging functions of PAR2 with the coagulation system in HCC progression remained unclear. The present study aimed to investigate the role of TF, FVII and PAR2 in tumor progression of HCC. The expressions of TF, FVII and PAR2 from HCC specimens were evaluated by immunohistochemical stains and western blotting. We found that the expression of FVII, but not TF and PAR2, directly related to the vascular invasion and the clinical staging. Importantly, a lower level of FVII expression was significantly associated with the longer disease-free survival. The addition of FVII but not TF induced the expression of PAR2 and phosphorylation of ERK1/2, whereas knockdown of FVII decreased PAR2 expression and ERK1/2 phosphorylation in HCC cell lines. Furthermore, levels of phosphor-TSC2 (Ser664) were increased after treatment with FVII and PAR2 agonist whereas these were significantly abolished in the presence of a potent and specific MEK/ERK inhibitor U0126. Moreover, mTOR knockdown highly reduced Hep3B migration, which could be reverted by FVII but not TF and PAR2. These results indicated that FVII/PAR2 signaling through MEK/ERK and TSC2 axis for mTOR activation has potent effects on the migration of HCC cells. In addition, FVII/PAR2 signaling elicits an mTOR-independent signaling, which promotes hepatoma cell migration in consistent with the clinical observations. Our study indicates that levels of FVII, but not TF, are associated with tumor migration and invasiveness in HCC, and provides clues that evaluation of FVII expression in HCC may be useful as a prognostic indicator in patients with HCC and may form an alternative target for further therapy.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
Date : 1 January 2016
Identification Number : 10.1038/cddiscovery.2015.51
Additional Information : © 2015 Cell Death Differentiation Association. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit by/4.0/ This is the author's accepted version.
Depositing User : Symplectic Elements
Date Deposited : 10 Nov 2015 18:54
Last Modified : 12 Jan 2016 16:44

Actions (login required)

View Item View Item


Downloads per month over past year

Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800