Evidence map›Paper›PMID 26528757›Full record

ArticleOncotarget2015

Identification of short-form RON as a novel intrinsic resistance mechanism for anti-MET therapy in MET-positive gastric cancer.

Zheng Wu, Zhe Zhang, Xiaoxiao Ge, Ying Lin, Congqi Dai, Jinjia Chang, Xinyang Liu, Ruixuan Geng, Chenchen Wang, Huan Chen and 3 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 42 citations in OpenAlex.

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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

13 authors at 2 institutions in 1 country.

Zheng WuDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Zhe ZhangDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Xiaoxiao GeDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Ying LinDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Congqi DaiDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Jinjia ChangDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Xinyang LiuDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Ruixuan GengDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Chenchen WangDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Huan ChenDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Menghong SunDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Weijian GuoDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Jin LiDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Shanghai Medical College of Fudan University · CNFudan University Shanghai Cancer Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the promising results from initial studies, there are significant limitations in the application of MET-targeted therapy in gastric cancer. Intrinsic resistance is one of the major obstacles. The aim of this study is to identify the responsible receptor tyrosine kinases (RTKs) that determine the unresponsiveness of MET inhibitor in MET-positive gastric cancer. through an RNA-interference-based functional screen targeting most human RTKs, we identified that activation of the fibroblast growth factor receptor 2 (FGFR2) and recepteur d'origine nantais (RON) pathways attenuated MET inhibitor-induced suppression of cell proliferation and migration. Notably, in the two forms of RON pathway activation, only upregulation of short-form RON (sf-RON), but not stimulation of full length RON with macrophage stimulating protein, conferred MET inhibitor resistance in vitro and in vivo. Furthermore, the profile of the gastric cancer samples observed that sf-RON was frequently upregulated in MET-positive gastric cancer. Our findings indicate that activation of the sf-RON signaling pathway represents a novel mechanism underlying MET inhibitor unresponsiveness. A combination strategy with drugs targeting both RON and MET pathways is believed to improve the efficacy of MET-targeted therapy.

Indexed as

AdenocarcinomaAnimalsApoptosisBlotting, WesternCell AdhesionCell MovementCell ProliferationDrug Resistance, NeoplasmFlow CytometryHumansImmunoenzyme TechniquesImmunoprecipitationLung NeoplasmsMaleMiceMice, NudeProto-Oncogene Proteins c-metReceptor Protein-Tyrosine KinasesRNA, MessengerRNA, Small InterferingRON proteindrug resistancegastric cancerMETRONtargeted therapy

Identifiers

PMID26528757
PMCPMC4747350
OpenAlexW2265359946

What OpenQuestion holds

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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.