Evidence map›Paper›PMID 26061747›Full record

ArticleOncotarget2015

Functional relevance of a six mesenchymal gene signature in epithelial-mesenchymal transition (EMT) reversal by the triple angiokinase inhibitor, nintedanib (BIBF1120).

Ruby Yun-Ju Huang, Kuee Theng Kuay, Tuan Zea Tan, Mohammad Asad, Hei Mui Tang, Aloysius Hsien Chun Ng, Jieru Ye, Vin Yee Chung, Jean Paul Thiery

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 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  5. ACancers · 2021
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  10. Transcriptomic Analysis Reveals Prognostic Molecular Signatures of Stage I Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
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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

9 authors at 4 institutions in 1 country.

Ruby Yun-Ju HuangDepartment of Obstetrics and Gynaecology, National University Health System, Singapore.
Kuee Theng KuayCancer Science Institute of Singapore, National University of Singapore, Singapore.
Tuan Zea TanCancer Science Institute of Singapore, National University of Singapore, Singapore.
Mohammad AsadDepartment of Obstetrics and Gynaecology, National University Health System, Singapore.
Hei Mui TangCancer Science Institute of Singapore, National University of Singapore, Singapore.
Aloysius Hsien Chun NgDean's Office, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Jieru YeCancer Science Institute of Singapore, National University of Singapore, Singapore.
Vin Yee ChungCancer Science Institute of Singapore, National University of Singapore, Singapore.
Jean Paul ThieryCancer Science Institute of Singapore, National University of Singapore, Singapore.
National University of Singapore · SGNational University Cancer Institute, Singapore · SGInstitute of Molecular and Cell Biology · SGNational University Health System · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epithelial-mesenchymal transition (EMT), a crucial mechanism in carcinoma progression, describes the process whereby epithelial cells lose their apico-basal polarity and junctional complexes and acquire a mesenchymal-like morphology. Several markers are considered to be authentic indicators of an epithelial or mesenchymal status; however, there is currently no comprehensive or systematic method with which to determine their functional relevance. Previously, we identified a 33-gene EMT signature comprising 25 epithelial and 6 mesenchymal genes that best describe this concept of the EMT spectrum. Here, we designed small-scale siRNA screens targeting these six mesenchymal signature genes (CD99L2, EMP3, ITGA5, SYDE1, VIM, ZEB1) to explore their functional relevance and their roles during EMT reversal by nintedanib (BIBF1120) in a mesenchymal-like SKOV3 ovarian cancer cell line. We found that neither cell proliferation nor cytotoxicity was affected by silencing any of these genes. SKOV3 cells expressing siRNA against mesenchymal genes (ZEB1, EMP3, CD99L2, ITGA5, and SYDE1) showed enhanced colony compaction (reduced inter-nuclear distance). Inductions of E-cadherin expression were only observed in SYDE1- and ZEB1-silenced SKOV3 cells. In addition, only SYDE1-silenced SKOV3 cells showed increased anoikis. Finally, we identified that SYDE1 and ZEB1 were down-regulated in nintedanib-treated SKOV3 cells and SYDE1- and ZEB1-silenced SKOV3 cells showed enhanced nintedanib-induced up-regulation of E-cadherin. Nintedanib-treated SKOV3 cells also showed colony compaction and decreases in EMT scores both in vitro and in vivo. We conclude that SYDE1 and ZEB1 are functionally relevant in EMT reversal. This study thus provides a proof-of-concept for the use of in vitro siRNA screening to explore the EMT-related functions of selected genes and their potential relevance in the discovery of EMT reversing drugs.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationEnzyme InhibitorsEpithelial-Mesenchymal TransitionFemaleHumansIndolesMiceMice, Inbred BALB CMice, NudeOvarian NeoplasmsTreatment OutcomeAntineoplastic AgentsEnzyme InhibitorsIndolesnintedanibEMT reversalepithelial-mesenchymal transition (EMT)nintedanibsiRNA screentriple angiokinase inhibitor

Identifiers

PMID26061747
PMCPMC4673149
OpenAlexW1714842717

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.