Evidence map›Paper›PMID 34138730›Full record

ArticleScience advances2021

Genome-scale CRISPR-Cas9 screen of Wnt/β-catenin signaling identifies therapeutic targets for colorectal cancer.

Chunhua Wan, Sylvia Mahara, Claire Sun, Anh Doan, Hui Kheng Chua, Dakang Xu, Jia Bian, Yue Li, Danxi Zhu, Dhanya Sooraj and 3 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.8field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 65 citations in OpenAlex.

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  12. Intratumor microbiota and colorectal cancer: Comprehensive and lucid review.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024
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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

13 authors at 3 institutions in 4 countries.

Chunhua WanCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.ORCID 0000-0002-1587-9383
Sylvia MaharaCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.ORCID 0000-0001-7261-1423
Claire SunCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.ORCID 0000-0002-2124-3074
Anh DoanCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.
Hui Kheng ChuaCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.ORCID 0000-0002-6047-4027
Dakang XuDepartment of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia.
Jia BianCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.ORCID 0000-0002-0338-1414
Yue LiFaculty of Medical Laboratory Science, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 200025 Shanghai, China.
Danxi ZhuCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.
Dhanya SoorajCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.
Tomasz CierpickiDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0003-2058-0658
Jolanta GrembeckaDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-6180-9095
Ron FiresteinCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia. ron.firestein@monash.edu.ORCID 0000-0002-5255-1838
Hudson Institute of Medical Research · AURuijin Hospital · CNUniversity of Michigan · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant activation of Wnt/β-catenin pathway is a key driver of colorectal cancer (CRC) growth and of great therapeutic importance. In this study, we performed comprehensive CRISPR screens to interrogate the regulatory network of Wnt/β-catenin signaling in CRC cells. We found marked discrepancies between the artificial TOP reporter activity and β-catenin-mediated endogenous transcription and redundant roles of T cell factor/lymphoid enhancer factor transcription factors in transducing β-catenin signaling. Compiled functional genomic screens and network analysis revealed unique epigenetic regulators of β-catenin transcriptional output, including the histone lysine methyltransferase 2A oncoprotein (KMT2A/Mll1). Using an integrative epigenomic and transcriptional profiling approach, we show that KMT2A loss diminishes the binding of β-catenin to consensus DNA motifs and the transcription of β-catenin targets in CRC. These results suggest that KMT2A may be a promising target for CRCs and highlight the broader potential for exploiting epigenetic modulation as a therapeutic strategy for β-catenin-driven malignancies.

Indexed as

beta CateninColorectal NeoplasmsCell Line, TumorCell ProliferationCRISPR-Cas SystemsGene Expression Regulation, NeoplasticHumansTCF Transcription FactorsWnt Signaling Pathwaybeta CateninTCF Transcription Factors

Identifiers

PMID34138730
PMCPMC8133758
OpenAlexW3163787125

What OpenQuestion holds

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LicenceCC BY-NC
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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.