Evidence map›Paper›PMID 23752180›Full record

ArticleOncogene2014

An siRNA screen identifies the GNAS locus as a driver in 20q amplified breast cancer.

I Garcia-Murillas, R Sharpe, A Pearson, J Campbell, R Natrajan, A Ashworth, N C Turner

Open access · bronzeAbstract read
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

23 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Chromosomal copy number amplification-driven Linc01711 contributes to gastric cancer progression through histone modification-mediated reprogramming of cholesterol metabolism.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024
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  7. Glucocorticoids rapidly activate cAMP production via GFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  8. Article
  9. Elevated expression of GNAS promotes breast cancer cell proliferation and migration via the PI3K/AKT/Snail1/E-cadherin axis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019
    Article
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  11. Article
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  14. Review
  15. Large G protein α-subunit XLαs limits clathrin-mediated endocytosis and regulates tissue iron levels in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. Article
  17. Article
  18. Review
  19. Endothelin-1 Pathway Polymorphisms and Outcomes in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2015
    Article
  20. Copy number analysis of ductal carcinoma in situ with and without recurrence.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2015
    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

7 authors at 3 institutions in 2 countries.

I Garcia-MurillasThe Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
R SharpeThe Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
A PearsonThe Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
J CampbellThe Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
R NatrajanThe Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
A AshworthThe Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
N C Turner1] The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK [2] Breast Unit, Royal Marsden Hospital, London, UK.
Institute of Cancer Research · GBBreast Cancer Now · GBBreast Cancer Research Foundation · US

Funding

Breast Cancer Now BREAST CANCER NOW RESEARCH CENTRECancer Research UK A10038
6 · The paper itself

Abstract

Poor-prognosis oestrogen receptor-positive breast cancer is characterised by the presence of high-level focal amplifications. We utilised a focused small interfering RNA screen in 14 breast cancer cell lines to define genes that were pathogenic in three genomic regions focally amplified in oestrogen receptor-positive breast cancer, 8p11-12, 11q13 and 20q. Silencing the GNAS locus, that encodes the G protein alpha stimulatory subunit Gαs, specifically reduced the growth of 20q amplified breast cancer cell lines. Examination of a publically available small hairpin RNA data set confirmed GNAS silencing to be selective for 20q amplified cancer cell lines. Cell lines with 20q amplification were found to overexpress specifically the extra long Gαs splice variant (XLαs). Overexpression of XLαs induced cAMP levels to a greater extent than Gαs, suggesting that amplification of the GNAS locus, and overexpression of the XLαs variant in particular, enhanced cAMP signalling. GNAS silencing in amplified cell lines reduced extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and conversely overexpression of exogenous XLαs in a non-amplified cell line increased MEK-ERK1/2 phosphorylation, identifying one potential downstream consequence of enhanced cAMP signalling. Our data indicate that amplification of the GNAS locus may contribute to the pathogenesis of breast cancer, and highlight a previously unrecognised role for the GNAS XLαs variant in cancer.

Indexed as

Blotting, WesternBreast NeoplasmsCell Line, TumorChromograninsChromosomes, Human, Pair 20FemaleFlow CytometryFluorescent Antibody TechniqueGene AmplificationGenetic LociGTP-Binding Protein alpha Subunits, GsHumansProtein IsoformsReverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingChromograninsGNAS protein, humanGTP-Binding Protein alpha Subunits, GsProtein IsoformsRNA, Small Interfering

Identifiers

PMID23752180
PMCPMC3970970
OpenAlexW2070111700

What OpenQuestion holds

Textmetadata
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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.