Evidence map›Paper›PMID 28811376›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epithelial ovarian cancer.

Michiko Kodama, Takahiro Kodama, Justin Y Newberg, Hiroyuki Katayama, Makoto Kobayashi, Samir M Hanash, Kosuke Yoshihara, Zhubo Wei, Jean C Tien, Roberto Rangel and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 3 pooled it
3.6field-weighted citation impact, top 6% 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

72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 108 citations in OpenAlex.

  1. Pooled it
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  10. VCP's nuclear journey: Initiated by interacting with KPNB1 to repair DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Antitumor potential of ivermectin against T-cell lymphoma-bearing hosts.Medical oncology (Northwood, London, England) · 2025
    Article
  12. Article
  13. Article
  14. Survival-Related Genes on Chromosomes 6 and 17 in Medulloblastoma.International journal of molecular sciences · 2024
    Article
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12 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

16 authors at 4 institutions in 2 countries.

Michiko KodamaCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
Takahiro KodamaCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030; t-kodama@gh.med.osaka-u.ac.jp njenkins1@mdanderson.org.ORCID 0000-0002-6250-1324
Justin Y NewbergCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
Hiroyuki KatayamaDepartment of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Makoto KobayashiDepartment of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Samir M HanashDepartment of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Kosuke YoshiharaDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 9518510, Japan.
Zhubo WeiCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
Jean C TienCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
Roberto RangelCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
Kae HashimotoDepartment of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 5650871, Japan.
Seiji MabuchiDepartment of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 5650871, Japan.
Kenjiro SawadaDepartment of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 5650871, Japan.
Tadashi KimuraDepartment of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 5650871, Japan.
Neal G CopelandCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
Nancy A JenkinsCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030; t-kodama@gh.med.osaka-u.ac.jp njenkins1@mdanderson.org.
Houston Methodist · USThe University of Osaka · JPThe University of Texas MD Anderson Cancer Center · USNiigata University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epithelial ovarian cancer (EOC) is a deadly cancer, and its prognosis has not been changed significantly during several decades. To seek new therapeutic targets for EOC, we performed an in vivo dropout screen in human tumor xenografts using a pooled shRNA library targeting thousands of druggable genes. Then, in follow-up studies, we performed a second screen using a genome-wide CRISPR/Cas9 library. These screens identified 10 high-confidence drug targets that included well-known oncogenes such as ERBB2 and RAF1, and novel oncogenes, notably KPNB1, which we investigated further. Genetic and pharmacological inhibition showed that KPNB1 exerts its antitumor effects through multiphase cell cycle arrest and apoptosis induction. Mechanistically, proteomic studies revealed that KPNB1 acts as a master regulator of cell cycle-related proteins, including p21, p27, and APC/C. Clinically, EOC patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1. Interestingly, ivermectin, a Food and Drug Administration-approved antiparasitic drug, showed KPNB1-dependent antitumor effects on EOC, serving as an alternative therapeutic toward EOC patients through drug repositioning. Last, we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC both in vitro and in vivo than either drug alone. Our studies have thus identified a combinatorial therapy for EOC, in addition to a plethora of potential drug targets.

Indexed as

Apoptosisbeta KaryopherinsCarcinoma, Ovarian EpithelialCell Cycle CheckpointsCell Cycle ProteinsCell Line, TumorCell ProliferationDrug Screening Assays, AntitumorFemaleGene Expression Regulation, NeoplasticHumansIvermectinLoss of Function MutationNeoplasms, Glandular and EpithelialOncogenesOvarian Neoplasmsbeta KaryopherinsCell Cycle ProteinsIvermectinKPNB1 protein, humanPaclitaxelRNA, Small InterferingCRISPR/CasKPNB1loss-of-function screenovarian cancerRNAi

Identifiers

PMID28811376
PMCPMC5584430
OpenAlexW2745505226

What OpenQuestion holds

Textmetadata
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.