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 accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V. J., Richardson, A. L., & Weinberg, R. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.034 · Cited by 3,759
Hu, Y., & Smyth, G. K. (2009) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.06.008 · Cited by 2,083
Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
Vermeulen, L., De Sousa E Melo, F., van der Heijden, M., Cameron, K., de Jong, J. H., Borovski, T., Tuynman, J. B., Todaro, M., Merz, C., Rodermond, H., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2048 · Cited by 1,804
Erez, N., Truitt, M., Olson, P., & Hanahan, D. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.041 · Cited by 1,515
NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma
Luedde, T., & Schwabe, R. F. (2011) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.213 · Cited by 1,345
Identification and Characterization of Tumorigenic Liver Cancer Stem/Progenitor Cells
Ma, S., Chan, K., Hu, L., Lee, T. K., Wo, J. Y., Ng, I. O., Zheng, B., & Guan, X. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.04.025 · Cited by 1,192
Self-citationSignificance of CD90+ Cancer Stem Cells in Human Liver Cancer
Yang, Z. F., Ho, D. W., Ng, M. N., Lau, C. K., Yu, W. C., Ngai, P., Chu, P. W. K., Lam, C. T., Poon, R. T. P., & Fan, S. T. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.01.013 · Cited by 1,188
Yamashita, T., Ji, J., Budhu, A., Forgues, M., Yang, W., Wang, H., Jia, H., Ye, Q., Qin, L., Wauthier, E., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2008.12.004 · Cited by 1,149
TUMOR STROMA AND REGULATION OF CANCER DEVELOPMENT
Tlsty, T. D., & Coussens, L. M. (2006) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.1.110304.100224 · Cited by 987
Drug development of MET inhibitors: targeting oncogene addiction and expedience
Comoglio, P. M., Giordano, S., & Trusolino, L. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2530 · Cited by 818
Cited by
Nieto, M. A., Huang, R. Y.-J., Jackson, R. A., & Thiery, J. P. (2016) · Cell · doi:10.1016/j.cell.2016.06.028 · Cited by 4,492
Targeting cancer stem cell pathways for cancer therapy
Yang, L., Shi, P., Zhao, G., Xu, J., Peng, W., Zhang, J., Zhang, G., Wang, X., Dong, Z., Chen, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0110-5 · Cited by 1,906
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265
Cancer stem cells as key drivers of tumour progression
Ayob, A. Z., & Ramasamy, T. S. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0426-4 · Cited by 910
Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer
Wu, F., Yang, J., Liu, J., Wang, Y., Mu, J., Zeng, Q., Deng, S., & Zhou, H. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00641-0 · Cited by 773
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)
- OpenAlex
- W2343063345
- Cited by
- 334
- References
- 30
- FWCI
- 18.82
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling. https://app.cochat.ai/papers/10.1016/j.celrep.2016.04.019
- The paper
- 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. (2016). Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling. Cell Reports. https://doi.org/10.1016/j.celrep.2016.04.019
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
