Evidence map›Paper›PMID 30360374›Full record

ArticleCancers2018

Choline Kinase Alpha Inhibition by EB-3D Triggers Cellular Senescence, Reduces Tumor Growth and Metastatic Dissemination in Breast Cancer.

Elena Mariotto, Giampietro Viola, Roberto Ronca, Luca Persano, Sanja Aveic, Zaver M Bhujwalla, Noriko Mori, Benedetta Accordi, Valentina Serafin, Luisa Carlota López-Cara and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.6field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 39 citations in OpenAlex.

  1. The role of phosphatidylcholine metabolism in tumors.Medical oncology (Northwood, London, England) · 2025
    Review
  2. Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025
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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 5 institutions in 3 countries.

Elena MariottoPediatric Hematooncology Laboratory, Department of Women's and Children's health, University of Padova, 35128 Padova, Italy. mariottoelena@gmail.com.ORCID 0000-0002-3960-8561
Giampietro ViolaPediatric Hematooncology Laboratory, Department of Women's and Children's health, University of Padova, 35128 Padova, Italy. giampietro.viola.1@unipd.it.
Roberto RoncaExperimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. roberto.ronca@unibs.it.ORCID 0000-0001-8979-7068
Luca PersanoPediatric Hematooncology Laboratory, Department of Women's and Children's health, University of Padova, 35128 Padova, Italy. luca.persano@unipd.it.
Sanja AveicFondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy. s.aveic@irpcds.org.ORCID 0000-0002-3886-4360
Zaver M BhujwallaIn Vivo Cellular Molecular Imaging Center Program, Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University, Baltimore, MD 21205, USA. zaver@mri.jhu.edu.
Noriko MoriIn Vivo Cellular Molecular Imaging Center Program, Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University, Baltimore, MD 21205, USA. noriko@mri.jhu.edu.
Benedetta AccordiPediatric Hematooncology Laboratory, Department of Women's and Children's health, University of Padova, 35128 Padova, Italy. benedetta.accordi@unipd.it.
Valentina SerafinPediatric Hematooncology Laboratory, Department of Women's and Children's health, University of Padova, 35128 Padova, Italy. valentina.serafin@unipd.it.
Luisa Carlota López-CaraDepartment of Pharmaceutical Chemistry and Organic, Faculty of Pharmacy, Cartuja Campus, University of Granada, 18011 Granada, Spain. lcarlotalopez@ugr.es.ORCID 0000-0003-1142-6448
Roberta BortolozziPediatric Hematooncology Laboratory, Department of Women's and Children's health, University of Padova, 35128 Padova, Italy. roberta.bortolozzi@unipd.it.ORCID 0000-0002-3357-4815
University of Padua · ITJohns Hopkins University · USCittà della Speranza Foundation · ITUniversidad de Granada · ESUniversity of Brescia · IT

Funding

Associazione Italiana per la Ricerca sul Cancro Fellowship n. 21101Fondazione Città della Speranza IRP13/05Fondazione Italiana per la Ricerca sul Cancro Fellowship n. 16616Universidad de Granada CEI2013-MP-1
6 · The paper itself

Abstract

Choline kinase (ChoK) is the first enzyme of the Kennedy pathway leading to the biosynthesis of phosphatidylcholine (PtdCho), the most abundant phospholipid in eukaryotic cell membranes. EB-3D is a novel choline kinase α1 (ChoKα1) inhibitor with potent antiproliferative activity against a panel of several cancer cell lines. ChoKα1 is particularly overexpressed and hyperactivated in aggressive breast cancer. By NMR analysis, we demonstrated that EB-3D is able to reduce the synthesis of phosphocholine, and using flow cytometry, immunoblotting, and q-RT-PCR as well as proliferation and invasion assays, we proved that EB-3D strongly impairs breast cancer cell proliferation, migration, and invasion. EB-3D induces senescence in breast cancer cell lines through the activation of the metabolic sensor AMPK and the subsequent dephosphorylation of mTORC1 downstream targets, such as p70S6K, S6 ribosomal protein, and 4E-BP1. Moreover, EB-3D strongly synergizes with drugs commonly used for breast cancer treatment. The antitumorigenic potential of EB-3D was evaluated in vivo in the syngeneic orthotopic E0771 mouse model of breast cancer, where it induces a significant reduction of the tumor mass at low doses. In addition, EB-3D showed an antimetastatic effect in experimental and spontaneous metastasis models. Altogether, our results indicate that EB-3D could be a promising new anticancer agent to improve aggressive breast cancer treatment protocols.

Indexed as

breast cancerCholine Kinase αsenescencesmall molecules

Identifiers

PMID30360374
PMCPMC6209942
OpenAlexW2896042812

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.