Evidence map›Paper›PMID 30572598›Full record

ArticleInternational journal of molecular sciences2018

High Throughput Chemical Screening Reveals Multiple Regulatory Proteins on FOXA1 in Breast Cancer Cell Lines.

Shixiong Wang, Sachin Kumar Singh, Madhumohan R Katika, Sandra Lopez-Aviles, Antoni Hurtado

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Sex Hormone Receptor Signals in Human Malignancies.International journal of molecular sciences · 2019
    Article
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

5 authors at 1 institution in 1 country.

Shixiong WangBreast Cancer Research group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, P.O. 1137 Blindern, 0318 Oslo, Norway. shixiong.wang@ncmm.uio.no.
Sachin Kumar SinghBreast Cancer Research group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, P.O. 1137 Blindern, 0318 Oslo, Norway. parmarsachinsingh@gmail.com.
Madhumohan R KatikaBreast Cancer Research group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, P.O. 1137 Blindern, 0318 Oslo, Norway. maddycdfd@gmail.com.
Sandra Lopez-AvilesCell Cycle Research group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, P.O. 1137 Blindern, 0318 Oslo, Norway. s.l.aviles@ncmm.uio.no.
Antoni HurtadoBreast Cancer Research group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, P.O. 1137 Blindern, 0318 Oslo, Norway. toni.hurtado@ncmm.uio.no.
University of Oslo · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Forkhead box A1 (FOXA1) belongs to the forkhead class transcription factor family, playing pioneering function for hormone receptors in breast and prostate cancers, and mediating activation of linage specific enhancers. Interplay between FOXA1 and breast cancer specific signaling pathways has been reported previously, indicating a regulation network on FOXA1 in breast cancer cells. Here in this study, we aimed to identify which are the proteins that could potentially control FOXA1 function in breast cancer cell lines expressing different molecular markers. We first established a luciferase reporter system reflecting FOXA1 binding to DNA. Then, we applied high throughput chemical screening of multiple protein targets and mass spectrometry in breast cancer cell lines expressing different molecular markers: ER positive/HER2 negative (MCF-7), ER positive/HER2 positive (BT474), and ER negative/HER2 positive (MDA-MB-453). Regardless of estrogen receptor status, HER2 (human epidermal growth factor receptor 2) enriched cell lines showed similar response to kinase inhibitors, indicating the control of FOXA1 by cell signaling kinases. Among these kinases, we identified additional receptor tyrosine kinases and cyclin-dependent kinases as regulators of FOXA1. Furthermore, we performed proteomics experiments from FOXA1 inmunoprecipitated protein complex to identify that FOXA1 interacts with several proteins. Among all the targets, we identified cyclin-dependent kinase 1 (CDK1) as a positive factor to interact with FOXA1 in BT474 cell line. In silico analyses confirmed that cyclin-dependent kinases might be the kinases responsible for FOXA1 phosphorylation at the Forkhead domain and the transactivation domain. These results reveal that FOXA1 is potentially regulated by multiple kinases. The cell cycle control kinase CDK1 might control directly FOXA1 by phosphorylation and other kinases indirectly by means of regulating other proteins.

Indexed as

CDC2 Protein KinaseCell Line, TumorGenes, ReporterHepatocyte Nuclear Factor 3-alphaHigh-Throughput Screening AssaysHumansLuciferasesProteomicsReproducibility of ResultsCDC2 Protein KinaseFOXA1 protein, humanHepatocyte Nuclear Factor 3-alphaLuciferasesbreast cancerdrug screening and proteomicsFOXA1

Identifiers

PMID30572598
PMCPMC6321185
OpenAlexW2904669629

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.