Evidence map›Paper›PMID 33767353›Full record

ArticleCommunications biology2021

A genome-scale CRISPR Cas9 dropout screen identifies synthetically lethal targets in SRC-3 inhibited cancer cells.

Yosi Gilad, Yossi Eliaz, Yang Yu, Adam M Dean, San Jung Han, Li Qin, Bert W O'Malley, David M Lonard

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.1field-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

10 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Yosi GiladDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Yossi EliazDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Yang YuDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Adam M DeanDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
San Jung HanDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0003-3692-6756
Li QinDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8476-3800
Bert W O'MalleyDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. berto@bcm.edu.ORCID http://orcid.org/0000-0003-3332-1399
David M LonardDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. dlonard@bcm.edu.
Baylor College of Medicine · US

Funding

REPRODUCTIVE HORMONES: BIOLOGICAL AND MOLECULAR ACTIONSR01HD008188 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI DAVID M LONARD, JOHN P LYDON · 1985 to 2026
$16.3M
SEX HORMONE RECEPTOR COMPONENTS AND THE CELL GENOMER01HD007857 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI DAVID M LONARD, JOHN P LYDON · 1985 to 2026
$14.6M
High Throughput Genomic Sequencer at BCM Core FacilityS10OD023469 · OD · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI · 2017 to 2017
$600k
Acquisition of the Fluidigm system to accelerate functional genomics researchS10OD018033 · OD · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI · 2014 to 2014
$396k
RAT PUP HUDDLING: INTEGRATING MODELS AND EXPERIMENTSF32HD008188 · NICHD · INDIANA UNIVERSITY BLOOMINGTON · PI SCHANK, JEFFREY C · 1996 to 1998
–
NICHD NIH HHS F32 HD008188NICHD NIH HHS R01 HD007857NICHD NIH HHS R01 HD008188NIH HHS S10 OD018033NIH HHS S10 OD023469
6 · The paper itself

Abstract

Steroid receptor coactivator 3 (SRC-3/NCoA3/AIB1), is a key regulator of gene transcription and it plays a central role in breast cancer (BC) tumorigenesis, making it a potential therapeutic target. Beyond its function as an important regulator of estrogen receptor transcriptional activity, SRC-3 also functions as a coactivator for a wide range of other transcription factors, suggesting SRC-3 inhibition can be beneficial in hormone-independent cancers as well. The recent discovery of a potent SRC-3 small molecule inhibitor, SI-2, enabled the further development of additional related compounds. SI-12 is an improved version of SI-2 that like SI-2 has anti-proliferative activity in various cancer types, including BC. Here, we sought to identify gene targets, that when inhibited in the presence of SI-12, would lead to enhanced BC cell cytotoxicity. We performed a genome-scale CRISPR-Cas9 screen in MCF-7 BC cells under conditions of pharmacological pressure with SI-12. A parallel screen was performed with an ER inhibitor, fulvestrant, to shed light on both common and distinct activities between SRC-3 and ERα inhibition. Bearing in mind the key role of SRC-3 in tumorigenesis of other types of cancer, we extended our study by validating potential hits identified from the MCF-7 screen in other cancer cell lines.

Indexed as

CRISPR-Cas SystemsCell Line, TumorHumansMCF-7 CellsNuclear Receptor Coactivator 3NCOA3 protein, humanNuclear Receptor Coactivator 3

Identifiers

PMID33767353
PMCPMC7994904
OpenAlexW3139221490

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.