Evidence map›Paper›PMID 32409632›Full record

ArticleScientific reports2020

Differential responses to kinase inhibition in FGFR2-addicted triple negative breast cancer cells: a quantitative phosphoproteomics study.

Debbie L Cunningham, Adil R Sarhan, Andrew J Creese, Katherine P B Larkins, Hongyan Zhao, Harriet R Ferguson, Katie Brookes, Anna A Marusiak, Helen J Cooper, John K Heath

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

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  13. Therapeutic Advances in Oncology.International journal of molecular sciences · 2021
    Review
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

10 authors at 4 institutions in 3 countries.

Debbie L CunninghamSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. d.cunningham@bham.ac.uk.
Adil R SarhanSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Andrew J CreeseSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Katherine P B LarkinsSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Hongyan ZhaoSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Harriet R FergusonSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Katie BrookesSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Anna A MarusiakSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Helen J CooperSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
John K HeathSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. J.K.Heath@bham.ac.uk.
University of Birmingham · GBSouthern Technical University · IQUniversity of Manchester · GBUniversity of Warsaw · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fibroblast Growth Factor (FGF) dependent signalling is frequently activated in cancer by a variety of different mechanisms. However, the downstream signal transduction pathways involved are poorly characterised. Here a quantitative differential phosphoproteomics approach, SILAC, is applied to identify FGF-regulated phosphorylation events in two triple- negative breast tumour cell lines, MFM223 and SUM52, that exhibit amplified expression of FGF receptor 2 (FGFR2) and are dependent on continued FGFR2 signalling for cell viability. Comparative Gene Ontology proteome analysis revealed that SUM52 cells were enriched in proteins associated with cell metabolism and MFM223 cells enriched in proteins associated with cell adhesion and migration. FGFR2 inhibition by SU5402 impacts a significant fraction of the observed phosphoproteome of these cells. This study expands the known landscape of FGF signalling and identifies many new targets for functional investigation. FGF signalling pathways are found to be flexible in architecture as both shared, and divergent, responses to inhibition of FGFR2 kinase activity in the canonical RAF/MAPK/ERK/RSK and PI3K/AKT/PDK/mTOR/S6K pathways are identified. Inhibition of phosphorylation-dependent negative-feedback pathways is observed, defining mechanisms of intrinsic resistance to FGFR2 inhibition. These findings have implications for the therapeutic application of FGFR inhibitors as they identify both common and divergent responses in cells harbouring the same genetic lesion and pathways of drug resistance.

Indexed as

ProteomicsCell Line, TumorGene OntologyHumansPhosphoproteinsProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 2Triple Negative Breast NeoplasmsPhosphoproteinsProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 2

Identifiers

PMID32409632
PMCPMC7224374
OpenAlexW3025846972

What OpenQuestion holds

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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.