Evidence map›Paper›PMID 32300176›Full record

ArticleOncogene2020

Genome-wide CRISPR screen uncovers a synergistic effect of combining Haspin and Aurora kinase B inhibition.

Min Huang, Xu Feng, Dan Su, Gang Wang, Chao Wang, Mengfan Tang, Adriana Paulucci-Holthauzen, Traver Hart, Junjie Chen

Open access · greenAbstract read
In one paragraph

Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 24 citations in OpenAlex.

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  18. CRISPR screen in cancer: status quo and future perspectives.American journal of cancer research · 2021
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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

9 authors at 1 institution in 1 country.

Min Huang *Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Xu Feng *Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Dan SuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0003-1468-3538
Gang WangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Chao WangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Mengfan TangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Adriana Paulucci-HolthauzenDepartment of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Traver HartDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Junjie ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. jchen8@mdanderson.org.
The University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Project 4: Coordinating Nucleolytic Pathways During Crosslink RepairP01CA193124 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WOOD, RICHARD D · 2017 to 2022
$9.6M
Define redundant functions of H2AX and NBS1 in DNA repairR01CA210929 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, JUNJIE · 2017 to 2022
$1.8M
NCI NIH HHS P01 CA193124NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA210929
6 · The paper itself

Abstract

Aurora kinases are a family of serine/threonine kinases vital for cell division. Because of the overexpression of Aurora kinases in a broad range of cancers and their important roles in mitosis, inhibitors targeting Aurora kinases have attracted attention in cancer therapy. VX-680 is an effective pan-Aurora kinase inhibitor; however, its clinical efficacy was not satisfying. In this study, we performed CRISPR/Cas9 screens to identify genes whose depletion shows synthetic lethality with VX-680. The top hit from these screens was GSG2 (also known as Haspin), a serine/threonine kinase that phosphorylates histone H3 at Thr-3 during mitosis. Moreover, both Haspin knockout and Haspin inhibitor-treated HCT116 cells were hypersensitive to VX-680. Furthermore, we showed that the synthetic lethal interaction between Haspin depletion and VX-680 was mediated by the inhibition of Haspin with Aurora kinase B (AURKB), but not with Aurora kinase A (AURKA). Strikingly, combined inhibition of Haspin and AURKB had a better efficacy than single-agent treatment in both head and neck squamous cell carcinoma and non-small cell lung cancer. Taken together, our findings have uncovered a synthetic lethal interaction between AURKB and Haspin, which provides a strong rationale for this combination therapy for cancer patients.

Indexed as

Aurora Kinase BCRISPR-Cas SystemsIntracellular Signaling Peptides and ProteinsNeoplasm ProteinsNeoplasmsProtein Serine-Threonine KinasesA549 CellsCyclopropanesGenome-Wide Association StudyHCT116 CellsHumansPiperazinesProtein Kinase InhibitorsPyrazolesPyrimidinesAURKB protein, humanAurora Kinase BCyclopropanesHASPIN protein, humanIntracellular Signaling Peptides and ProteinsNeoplasm ProteinsPiperazinesProtein Kinase InhibitorsProtein Serine-Threonine KinasesPyrazolesPyrimidinestozasertib

Identifiers

PMID32300176
PMCPMC7291820
OpenAlexW3016698209

What OpenQuestion holds

Textmetadata
LicenceTDM
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.