Evidence map›Paper›PMID 29684792›Full record

ArticleTranslational oncology2018

Global Effects of DDX3 Inhibition on Cell Cycle Regulation Identified by a Combined Phosphoproteomics and Single Cell Tracking Approach.

Marise R Heerma van Voss, Kai Kammers, Farhad Vesuna, Justin Brilliant, Yehudit Bergman, Saritha Tantravedi, Xinyan Wu, Robert N Cole, Andrew Holland, Paul J van Diest and 1 more

Open access · goldAbstract read
In one paragraph

Article in Translational oncology, 2018. 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
1.4field-weighted citation impact, top 19% 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, 29 citations in OpenAlex.

  1. RNA helicase DDX3X promotes NK cell survival by supporting MCL1 expression.Journal of immunology (Baltimore, Md. : 1950) · 2025
    Article
  2. Role of DEAD/DEAH-box helicases in immunity, infection and cancers.Cell communication and signaling : CCS · 2025
    Review
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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

11 authors at 2 institutions in 2 countries.

Marise R Heerma van VossDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Kai KammersDivision of Biostatistics and Bioinformatics, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Farhad VesunaDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Justin BrilliantDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Yehudit BergmanDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Saritha TantravediDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Xinyan WuMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Robert N ColeMass Spectrometry and Proteomics Core, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Andrew HollandDepartment of Molecular Biology and Genetics, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Paul J van DiestDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Venu RamanDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. Electronic address: vraman2@jhmi.edu.
Johns Hopkins University · USUniversity Medical Center Utrecht · NL

Funding

Centrosome biogenesis and copy number controlR01GM114119 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI CORMACK, BRENDAN · 2015 to 2023
$3.3M
Analytical determination of biomarkers for diagnosis of breast cancer metastatic progressionR01CA207208 · NCI · JOHNS HOPKINS UNIVERSITY · PI RAMAN, VENU · 2016 to 2020
$1.8M
NCI NIH HHS R01 CA207208NIGMS NIH HHS R01 GM114119
6 · The paper itself

Abstract

DDX3 is an RNA helicase with oncogenic properties. The small molecule inhibitor RK-33 is designed to fit into the ATP binding cleft of DDX3 and hereby block its activity. RK-33 has shown potent activity in preclinical cancer models. However, the mechanism behind the antineoplastic activity of RK-33 remains largely unknown. In this study we used a dual phosphoproteomic and single cell tracking approach to evaluate the effect of RK-33 on cancer cells. MDA-MB-435 cells were treated for 24 hours with RK-33 or vehicle control. Changes in phosphopeptide abundance were analyzed with quantitative mass spectrometry using isobaric mass tags (Tandem Mass Tags). At the proteome level we mainly observed changes in mitochondrial translation, cell division pathways and proteins related to cell cycle progression. Analysis of the phosphoproteome indicated decreased CDK1 activity after RK-33 treatment. To further evaluate the effect of DDX3 inhibition on cell cycle progression over time, we performed timelapse microscopy of Fluorescent Ubiquitin Cell Cycle Indicators labeled cells after RK-33 or siDDX3 exposure. Single cell tracking indicated that DDX3 inhibition resulted in a global delay in cell cycle progression in interphase and mitosis. In addition, we observed an increase in endoreduplication. Overall, we conclude that DDX3 inhibition affects cells in all phases and causes a global cell cycle progression delay.

Identifiers

PMID29684792
PMCPMC6050443
OpenAlexW2800897838

What OpenQuestion holds

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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.