Evidence map›Paper›PMID 28604763›Full record

ArticleOncogenesis2017

Proline-Rich Homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth.

R M Kershaw, D Roberts, J Wragg, A M Shaaban, E Humphreys, J Halsall, L Price, R Bicknell, K Gaston, P-S Jayaraman

Open access · goldAbstract read
In one paragraph

Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 25% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
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  11. Targeting protein kinase CK2 in the treatment of cholangiocarcinoma.Exploration of targeted anti-tumor therapy · 2021
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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

10 authors at 2 institutions in 1 country.

R M KershawInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
D RobertsInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
J WraggInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
A M ShaabanInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
E HumphreysInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
J HalsallInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
L PriceInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
R BicknellInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
K GastonSchool of Biochemistry, University of Bristol, Bristol, UK.
P-S JayaramanInstitute of Cancer and Genome Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
University of Birmingham · GBUniversity of Bristol · GB

Funding

Medical Research Council MR/N012615/1
6 · The paper itself

Abstract

Breast tumours progress from hyperplasia to ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). PRH/HHEX (proline-rich homeodomain/haematopoietically expressed homeobox) is a transcription factor that displays both tumour suppressor and oncogenic activity in different disease contexts; however, the role of PRH in breast cancer is poorly understood. Here we show that nuclear localization of the PRH protein is decreased in DCIS and IBC compared with normal breast. Our previous work has shown that PRH phosphorylation by protein kinase CK2 prevents PRH from binding to DNA and regulating the transcription of multiple genes encoding growth factors and growth factor receptors. Here we show that transcriptionally inactive phosphorylated PRH is elevated in DCIS and IBC compared with normal breast. To determine the consequences of PRH loss of function in breast cancer cells, we generated inducible PRH depletion in MCF-7 cells. We show that PRH depletion results in increased MCF-7 cell proliferation in part at least due to increased vascular endothelial growth factor signalling. Moreover, we demonstrate that PRH depletion increases the formation of breast cancer cells with cancer stem cell-like properties. Finally, and in keeping with these findings, we show that PRH overexpression inhibits the growth of mammary tumours in mice. Collectively, these data indicate that PRH plays a tumour suppressive role in the breast and they provide an explanation for the finding that low PRH mRNA levels are associated with a poor prognosis in breast cancer.

Identifiers

PMID28604763
PMCPMC5519192
OpenAlexW2621496114

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.