Evidence map›Paper›PMID 30287279›Full record

ArticleCellular signalling2019

Epidermal growth factor can signal via β-catenin to control proliferation of mesenchymal stem cells independently of canonical Wnt signalling.

Charlotte Knight, Sally James, David Kuntin, James Fox, Katherine Newling, Sam Hollings, Rebecca Pennock, Paul Genever

Open access · hybridAbstract read
In one paragraph

Article in Cellular signalling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 38 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

8 authors at 1 institution in 1 country.

Charlotte KnightDepartment of Biology, University of York, York YO10 5DD, United Kingdom.
Sally JamesDepartment of Biology, University of York, York YO10 5DD, United Kingdom.
David KuntinDepartment of Biology, University of York, York YO10 5DD, United Kingdom.
James FoxDepartment of Biology, University of York, York YO10 5DD, United Kingdom.
Katherine NewlingDepartment of Biology, University of York, York YO10 5DD, United Kingdom.
Sam HollingsDepartment of Biology, University of York, York YO10 5DD, United Kingdom.
Rebecca PennockDepartment of Biology, University of York, York YO10 5DD, United Kingdom.
Paul GeneverDepartment of Biology, University of York, York YO10 5DD, United Kingdom. Electronic address: paul.genever@york.ac.uk.
University of York · GB

Funding

Arthritis Research UK 19429Arthritis Research UK 20575Biotechnology and Biological Sciences Research CouncilMedical Research CouncilVersus Arthritis 20575
6 · The paper itself

Abstract

Bone marrow mesenchymal stem/stromal cells (MSCs) maintain bone homeostasis and repair through the ability to expand in response to mitotic stimuli and differentiate into skeletal lineages. Signalling mechanisms that enable precise control of MSC function remain unclear. Here we report that by initially examining differences in signalling pathway expression profiles of individual MSC clones, we identified a previously unrecognised signalling mechanism regulated by epidermal growth factor (EGF) in primary human MSCs. We demonstrate that EGF is able to activate β-catenin, a key component of the canonical Wnt signalling pathway. EGF is able to induce nuclear translocation of β-catenin in human MSCs but does not drive expression of Wnt target genes or T cell factor (TCF) activity in MSC reporter cell lines. Using an efficient Design of Experiments (DoE) statistical analysis, with different combinations and concentrations of EGF and Wnt ligands, we were able to confirm that EGF does not influence the Wnt/β-catenin pathway in MSCs. We show that the effects of EGF on MSCs are temporally regulated to initiate early "classical" EGF signalling mechanisms (e.g via mitogen activated protein kinase) with delayed activation of β-catenin. By RNA-sequencing, we identified gene sets that were exclusively regulated by the EGF/β-catenin pathway, which were distinct from classical EGF-regulated genes. However, subsets of classical EGF gene targets were significantly influenced by EGF/β-catenin activation. These signalling pathways cooperate to enable EGF-mediated proliferation of MSCs by alleviating the suppression of cell cycle pathways induced by classical EGF signalling.

Indexed as

Wnt Signaling Pathwaybeta CateninCell LineCell ProliferationEpidermal Growth FactorHumansMesenchymal Stem Cellsbeta CateninCTNNB1 protein, humanEpidermal Growth FactorEpidermal growth factorIntegrin-linked kinaseMesenchymal stem cellsβ-Catenin

Identifiers

PMID30287279
PMCPMC6293317
OpenAlexW2895079804

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.