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 |
Issue Date: | 10-May-2016 | Source: | Cell reports, 5 May 2016, v. 15, no. 6, p. 1175-1189 | 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. | Keywords: | Cancer-associated fibroblasts (CAFs) FRA1 Hepatocyte growth factor (HGF) HEY1 Tumor-initiating cells (T-ICs) |
Publisher: | Cell Press | Journal: | Cell reports | ISSN: | 2211-1247 | DOI: | 10.1016/j.celrep.2016.04.019 | Rights: | © 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). The following publication Lau, E. Y. T., Lo, J., Cheng, B. Y. L., Ma, M. K. F., Lee, J. M. F., Ng, J. K. Y., ... & Ng, I. O. L. (2016). Cancer-associated fibroblasts regulate tumor-initiating cell plasticity in hepatocellular carcinoma through c-Met/FRA1/HEY1 signaling. Cell reports, 15(6), 1175-1189 is available at https://doi.org/10.1016/j.celrep.2016.04.019 |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Lau_Cancer-associated_fibroblasts.html | 74.56 kB | HTML | View/Open |
Page views
147
Last Week
0
0
Last month
Citations as of Apr 14, 2024
Downloads
80
Citations as of Apr 14, 2024
SCOPUSTM
Citations
234
Last Week
1
1
Last month
Citations as of Apr 5, 2024
WEB OF SCIENCETM
Citations
234
Last Week
0
0
Last month
Citations as of Apr 18, 2024
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.