Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/61389
Title: Cancer-associated fibroblasts regulate tumor-initiating cell plasticity in hepatocellular carcinoma through c-Met/FRA1/HEY1 signaling
Authors: Lau, EYT
Lo, J
Cheng, BYL
Ma, MKF
Lee, JMF
Ng, JKY
Chai, S
Lin, CH
Tsang, SY
Ma, S
Ng, IOL
Lee, TKW
Keywords: Cancer-associated fibroblasts (CAFs)
FRA1
Hepatocyte growth factor (HGF)
HEY1
Tumor-initiating cells (T-ICs)
Issue Date: 2016
Publisher: Cell Press
Source: Cell reports, 2016, v. 15, no. 6, p. 1175-1189 How to cite?
Journal: Cell reports 
Abstract: Like normal stem cells, tumor-initiating cells (T-ICs) are regulated extrinsically within the tumor microenvironment. Because HCC develops primarily in the context of cirrhosis, in which there is an enrichment of activated fibroblasts, we hypothesized that cancer-associated fibroblasts (CAFs) would regulate liver T-ICs. We found that the presence of α-SMA(+) CAFs correlates with poor clinical outcome. CAF-derived HGF regulates liver T-ICs via activation of FRA1 in an Erk1,2-dependent manner. Further functional analysis identifies HEY1 as a direct downstream effector of FRA1. Using the STAM NASH-HCC mouse model, we find that HGF-induced FRA1 activation is associated with the fibrosis-dependent development of HCC. Thus, targeting the CAF-derived, HGF-mediated c-Met/FRA1/HEY1 cascade may be a therapeutic strategy for the treatment of HCC.
URI: http://hdl.handle.net/10397/61389
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.04.019
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