Evidence map›Paper›PMID 25673823›Full record

ArticleMolecular cancer therapeutics2015

Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity.

Rosemarie C D'Angelo, Maria Ouzounova, April Davis, Daejin Choi, Stevie M Tchuenkam, Gwangil Kim, Tahra Luther, Ahmed A Quraishi, Yasin Senbabaoglu, Sarah J Conley and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
8.3field-weighted citation impact, top 1% 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

69 citing papers in PubMed, 120 citations in OpenAlex.

  1. Review
  2. The miRNA-4330/ABCG2 axis overcomes drug resistance and cancer progression in both ER-positive and ER-negative resistant breast cancer cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  16. Article
  17. Tumour Stem Cells in Breast Cancer.International journal of molecular sciences · 2022
    Review
  18. Modulation of Notch Signaling Pathway by Bioactive Dietary Agents.International journal of molecular sciences · 2022
    Review
  19. Review
  20. Review

9 more citing papers are in PubMed but not listed here.

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

14 authors at 2 institutions in 2 countries.

Rosemarie C D'Angelo *
Maria Ouzounova *
April Davis
Daejin ChoiGeorgia Regents University Cancer Center, Department of Biochemistry and Molecular Biology 1410 Laney Walker Blvd. CN2136 Augusta, GA 30912.
Stevie M TchuenkamGeorgia Regents University Cancer Center, Department of Biochemistry and Molecular Biology 1410 Laney Walker Blvd. CN2136 Augusta, GA 30912.
Gwangil Kim
Tahra Luther
Ahmed A Quraishi
Yasin Senbabaoglu
Sarah J Conley
Shawn G Clouthier
Khaled A Hassan
Max S Wicha
Hasan Korkaya
Michigan Center for Translational Pathology · USMemorial Sloan Kettering Cancer Center · US

Funding

Regulation of Breast Stem Cells by the MicroenvironmentR01CA101860 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WICHA, MAX S. · 2004 to 2013
$2.4M
Stem Cell Self-Renewal mammary CarcinogenesisR01CA129765 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WICHA, MAX S. · 2008 to 2015
$2.4M
NCI NIH HHS CA101860NCI NIH HHS CA129765NCI NIH HHS R01 CA101860NCI NIH HHS R01 CA129765
6 · The paper itself

Abstract

Developmental pathways such as Notch play a pivotal role in tissue-specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch(+)) or reduced activity (Notch(-)) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays, we investigated the role of the Notch pathway in breast CSC regulation. Breast cancer cells with increased Notch activity displayed increased sphere formation as well as expression of breast CSC markers. Interestingly Notch(+) cells displayed higher Notch4 expression in both basal and luminal breast cancer cell lines. Moreover, Notch(+) cells demonstrated tumor initiation capacity at serial dilutions in mouse xenografts, whereas Notch(-) cells failed to generate tumors. γ-Secretase inhibitor (GSI), a Notch blocker but not a chemotherapeutic agent, effectively targets these Notch(+) cells in vitro and in mouse xenografts. Furthermore, elevated Notch4 and Hey1 expression in primary patient samples correlated with poor patient survival. Our study revealed a molecular mechanism for the role of Notch-mediated regulation of breast CSCs and provided a compelling rationale for CSC-targeted therapeutics.

Indexed as

Amyloid Precursor Protein SecretasesAnimalsAntineoplastic AgentsBasic Helix-Loop-Helix ProteinsBreast NeoplasmsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHeterograftsHumansMCF-7 CellsMiceMice, Inbred NODMice, NudeMice, SCIDNeoplastic Stem CellsAmyloid Precursor Protein SecretasesAntineoplastic AgentsBasic Helix-Loop-Helix ProteinsHairy, HRT1 proteinReceptors, NotchRepressor Proteins

Identifiers

PMID25673823
PMCPMC4456218
OpenAlexW2060649255

What OpenQuestion holds

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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.