Evidence map›Paper›PMID 28069043›Full record

ArticleJournal of experimental & clinical cancer research : CR2017

FGF19/FGFR4 signaling contributes to the resistance of hepatocellular carcinoma to sorafenib.

Lixia Gao, Xuli Wang, Yaoliang Tang, Shuang Huang, Chien-An Andy Hu, Yong Teng

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 174 citations in OpenAlex.

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  15. Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Lixia GaoDepartment of Oral Biology, Dental College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.
Xuli WangDepartment of Radiology and Imaging Sciences, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Yaoliang TangVascular Biology Center, Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Shuang HuangDepartment of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL, USA.
Chien-An Andy HuDepartment of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Yong TengDepartment of Oral Biology, Dental College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA. yteng@augusta.edu.
Augusta University · USHuntsman Cancer Institute · USUniversity of Florida · USUniversity of New Mexico · US

Funding

Notch1/miR-322 Axis in Stem Cell Mediated Vascular RepairR01HL134354 · NHLBI · AUGUSTA UNIVERSITY · PI ASHRAF, MUHAMMAD, TANG, YAO LIANG · 2016 to 2020
$2.5M
6 · The paper itself

Abstract

backgroundSorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to sorafenib therapy.

methodsFGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9. Protein levels of FGF19, FGFR4 and c-PARP in various HCC cell lines were measured by Western blotting analysis. Cell viability was determined by MTS assay, apoptosis was determined by DAPI nuclear staining and Western blot of c-PRAP, and ROS generation was determined by DCFH-DA staining and electrochemical biosensor.

resultsWe showed that FGF19, when overexpressed, inhibited the effect of sorafenib on ROS generation and apoptosis in HCC. In contrast, loss of FGF19 or its receptor FGFR4 led to a remarkable increase in sorafenib-induced ROS generation and apoptosis. In addition, knockdown of FGF19 in sorafenib-resistant HCC cells significantly enhanced the sensitivity to sorafenib. Importantly, targeting FGF19/FGFR4 axis by ponatinib, a third-generation inhibitor of chronic myeloid leukemia, overcomes HCC resistance of sorafenib by enhancing ROS-associated apoptosis in sorafenib-treated HCC.

conclusionOur results provide the first evidence that inhibition of FGF19/FGFR4 signaling significantly overcomes sorafenib resistance in HCC. Co-treatment of ponatinib and sorafinib may represent an effective therapeutic approach for eradicating HCC.

Indexed as

Drug Resistance, NeoplasmCarcinoma, HepatocellularCell Line, TumorCell SurvivalFibroblast Growth FactorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHep G2 CellsHumansLiver NeoplasmsNiacinamidePhenylurea CompoundsReactive Oxygen SpeciesReceptor, Fibroblast Growth Factor, Type 4Signal TransductionSorafenibFGF19 protein, humanFGFR4 protein, humanFibroblast Growth FactorsNiacinamidePhenylurea CompoundsReactive Oxygen SpeciesReceptor, Fibroblast Growth Factor, Type 4SorafenibDrug resistanceFGF19FGFR4Hepatocellular carcinomaSorafenibSynergistic effect

Identifiers

PMID28069043
PMCPMC5223586
OpenAlexW2570752112

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.