Evidence map›Paper›PMID 29720215›Full record

ArticleBreast cancer research : BCR2018

Dependence receptor UNC5A restricts luminal to basal breast cancer plasticity and metastasis.

Maria B Padua, Poornima Bhat-Nakshatri, Manjushree Anjanappa, Mayuri S Prasad, Yangyang Hao, Xi Rao, Sheng Liu, Jun Wan, Yunlong Liu, Kyle McElyea and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Review
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  14. Genetic Ancestry-dependent Differences in Breast Cancer-induced Field Defects in the Tumor-adjacent Normal Breast.Clinical cancer research : an official journal of the American Association for Cancer Research · 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

15 authors.

Maria B PaduaDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Poornima Bhat-NakshatriDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Manjushree AnjanappaDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Mayuri S PrasadDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Yangyang HaoDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Xi RaoDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Jun WanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Yunlong LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Kyle McElyeaDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Max JacobsenDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
George SanduskyDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Sandra AlthouseDepartment of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Susan PerkinsDepartment of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Harikrishna NakshatriDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. hnakshat@iupui.edu.ORCID 0000-0001-8876-0052

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe majority of estrogen receptor-positive (ERα

methodsWe used short hairpin (sh)RNA and/or the CRISPR/Cas9 system to knockdown the expression of the dependence receptor UNC5A in ERα

resultsKnockdown of the E2-inducible UNC5A resulted in altered basal gene expression affecting plasma membrane integrity and ERα signaling, as evident from ligand-independent activity of ERα, altered turnover of phosphorylated ERα, unique E2-dependent expression of genes effecting histone demethylase activity, enhanced upregulation of E2-inducible genes such as BCL2, and E2-independent tumorigenesis accompanied by multiorgan metastases. UNC5A depletion led to the appearance of a luminal/basal hybrid phenotype supported by elevated expression of basal/stem cell-enriched ∆Np63, CD44, CD49f, epidermal growth factor receptor (EGFR), and the lymphatic vessel permeability factor NTN4, but lower expression of luminal/alveolar differentiation-associated ELF5 while maintaining functional ERα. In addition, UNC5A-depleted cells acquired bipotent luminal progenitor characteristics based on KRT14

conclusionThese studies reveal an unexpected role of the axon guidance receptor UNC5A in fine-tuning ERα and EGFR signaling and the luminal progenitor status of hormone-sensitive breast cancers. Furthermore, UNC5A knockdown cells provide an ideal model system to investigate metastasis of ERα

Indexed as

Breast NeoplasmsCarcinogenesisCell PlasticityCRISPR-Cas SystemsErbB ReceptorsEstrogen Receptor alphaFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansMCF-7 CellsNeoplasm MetastasisNetrin ReceptorsReceptors, Cell SurfaceRNA, Small InterferingEGFR protein, humanErbB ReceptorsESR1 protein, humanEstrogen Receptor alphaNetrin ReceptorsReceptors, Cell SurfaceRNA, Small InterferingUNC5A protein, humanBreast cancerEstradiol and metastasisEstrogen receptorNetrin-1UNC5A

Identifiers

PMID29720215
PMCPMC5932758

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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.