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Cited by 334

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling

Open access
Lau, Eunice Yuen Ting, Lo, Jessica, Cheng, Bowie Yik Ling, Ma, Mark Kin Fai, Lee, Joyce Man Fong, Ng, Johnson Kai Yu, Chai, Stella, Lin, Chi Ho, Tsang, Suk Ying, Ma, Stephanie, Ng, Irene Oi Lin, Lee, Terence Kin Wah·2016·Cell Reports
DOI 10.1016/j.celrep.2016.04.019
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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.

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Crossref · 10.1016/j.celrep.2016.04.019

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Metadata

Authors
Lau, E. Y. T., Lo, J., Cheng, B. Y. L., Ma, M. K. F., Lee, J. M. F., Ng, J. K. Y., Chai, S., Lin, C. H., Tsang, S. Y., Ma, S., Ng, I. O. L., & Lee, T. K. W.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2016-05
Volume
15
Issue
6
Pages
1175-1189
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2016.04.019
OpenAlex
W2343063345
Cited by
334
References
30
FWCI
18.82
Type
journal article
Language
en
Open access
gold

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.