Evidence map›Paper›PMID 26790028›Full record

ArticleCancer science2016

Elevated hepatocyte growth factor expression as an autocrine c-Met activation mechanism in acquired resistance to sorafenib in hepatocellular carcinoma cells.

Zeynep Firtina Karagonlar, Dogukan Koc, Evin Iscan, Esra Erdal, Neşe Atabey

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

Article in Cancer science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
8.2field-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

77 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.

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  4. Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study.Annals of oncology : official journal of the European Society for Medical Oncology · 2017
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17 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

5 authors at 1 institution in 1 country.

Zeynep Firtina KaragonlarFaculty of Engineering and Computer Science, Izmir University of Economics, Izmir.
Dogukan KocIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir.
Evin IscanIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir.
Esra ErdalIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir.
Neşe AtabeyIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir.
Dokuz Eylül University · TR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related deaths worldwide. Limitations in HCC treatment result due to poor prognosis and resistance against traditional radiotherapy and chemotherapies. The multikinase inhibitor sorafenib is the only FDA approved drug available for advanced HCC patients, and development of second-line treatment options for patients who cannot tolerate or develop resistance to sorafenib is an urgent medical need. In this study, we established sorafenib-resistant cells from Huh7 and Mahlavu cell lines by long-term sorafenib exposure. Sorafenib-resistant HCC cells acquired spindle-shape morphology, upregulated mesenchymal markers, and showed significant increase in both migration and invasion abilities compared to their parental counterparts. Moreover, after long-term sorafenib treatment, HCC cells showed induction of hepatocyte growth factor (HGF) synthesis and secretion along with increased levels of c-Met kinase and its active phosphorylated form, indicating autocrine activation of HGF/c-Met signaling. Importantly, the combined treatment of the resistant cells with c-Met kinase inhibitor SU11274 and HGF neutralizing antibody significantly reversed the increased invasion ability of the cells. The combined treatment also significantly augmented sorafenib-induced apoptosis, suggesting restoration of sorafenib sensitivity. These results describe, for the first time, compensatory upregulation of HGF synthesis leading to autocrine activation of HGF/c-Met signaling as a novel cellular strategy in the acquisition of sorafenib resistance. Therefore, we suggest that combinatorial therapeutic strategies with HGF and c-Met inhibitors comprise promising candidates for overcoming sorafenib resistance.

Indexed as

Antibodies, NeutralizingApoptosisAutocrine CommunicationCarcinoma, HepatocellularCell Line, TumorCell ProliferationDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHepatocyte Growth FactorHumansIndolesLiver NeoplasmsNiacinamidePhenylurea CompoundsPiperazinesProto-Oncogene Proteins c-met((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide)Antibodies, NeutralizingHepatocyte Growth FactorIndolesNiacinamidePhenylurea CompoundsPiperazinesProto-Oncogene Proteins c-metSorafenibSulfonamidesc-Methepatocarcinogenesishepatocyte growth factorliver cancersorafenib

Identifiers

PMID26790028
PMCPMC4832867
OpenAlexW2289555820

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.