Evidence map›Paper›PMID 33167919›Full record

ArticleBMC cancer2020

EP300 knockdown reduces cancer stem cell phenotype, tumor growth and metastasis in triple negative breast cancer.

Alexander Ring, Pushpinder Kaur, Julie E Lang

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 10% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

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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

3 authors at 1 institution in 2 countries.

Alexander RingDivision of Surgical Oncology, Department of Surgery and University of Southern California Norris Cancer Center, University of Southern California, Los Angeles, CA, USA. alexander.ring@usz.ch.ORCID http://orcid.org/0000-0002-0092-1323
Pushpinder KaurDivision of Surgical Oncology, Department of Surgery and University of Southern California Norris Cancer Center, University of Southern California, Los Angeles, CA, USA.
Julie E LangDivision of Surgical Oncology, Department of Surgery and University of Southern California Norris Cancer Center, University of Southern California, Los Angeles, CA, USA.
University of Southern California · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
California Institute for Regenerative Medicine TG2-01161NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089
6 · The paper itself

Abstract

backgroundTriple negative breast cancer (TNBC) is an aggressive breast cancer subtype with basal features, lacking the expression of receptors targeted successfully in other breast cancer subtypes. Treatment response to adjuvant and neoadjuvant chemotherapy is often short-lived and metastatic spread occurs at higher rates than other subtypes within the first five years after diagnosis. TNBCs exhibit stem cell features and are enriched for cancer stem cell (CSC) populations. E1A Binding Protein P300 (EP300) is a large protein with multiple cellular functions, including as an effector in stem cell biology.

methodsWe used a genetic knockdown (KD) model of EP300 in TNBC cell lines to investigate the effect on CSC phenotype, tumor growth and metastasis. Side population assay and tumorsphere suspension culture were used in vitro. Xenograft mouse models were used for in vivo studies. We performed in silico analysis of publicly available gene expression data sets to investigate CSC gene expression and molecular pathways as well as survival outcomes associated with EP300 expression in patients with TNBC and basal-like BC.

resultsEP300 KD abolished the CSC phenotype by reducing ABCG2 expression, side population cells and tumorsphere formation capacity in vitro as well as tumor formation in a xenograft mouse model in vivo. Metastatic capacity was markedly reduced in EP300 KD cells in vivo, with no detection of circulating tumor cells. TCGA data analysis demonstrated that genes positively correlated with EP300 expression in TNBC and basal-like BC were associated with CSC biology. Survival analysis demonstrated that EP300 expression predicts poor recurrence free survival in TNBC and basal BC.

conclusionWe report a novel oncogenic role for EP300 in driving CSC phenotype representing a potential target to address tumor initiation and metastatic spread in TNBC and basal-like BC. EP300 might serve as a prognostic marker and potential therapeutic target in TNBC.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsApoptosisBiomarkers, TumorCell CycleCell MovementCell ProliferationE1A-Associated p300 ProteinFemaleHumansLymphatic MetastasisMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsPhenotypeBiomarkers, TumorE1A-Associated p300 ProteinEP300 protein, humanATP-binding cassette super-family G member 2 (ABCG2)/breast Cancer resistance protein (BCRP)Basal-like BCCancer stem cells (CSC)E1A-associated protein p300 (EP300)MetastasisTriple negative breast cancer (TNBC)

Identifiers

PMID33167919
PMCPMC7653866
OpenAlexW3100783618

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.