Evidence map›Paper›PMID 32300104›Full record

ArticleSignal transduction and targeted therapy2020

Pleiotropic tumor suppressor functions of WWOX antagonize metastasis.

Saleh Khawaled, Giovanni Nigita, Rosario Distefano, Sara Oster, Sung-Suk Suh, Yoav Smith, Abed Khalaileh, Yong Peng, Carlo M Croce, Tamar Geiger and 2 more

Open access · goldAbstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2020. 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
5.0field-weighted citation impact, top 4% 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, 37 citations in OpenAlex.

  1. WWOX maintains epidermal identity and suppresses EMT to prevent aggressive cutaneous squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  7. Involvement of FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p in breast cancer.Cancer biomarkers : section A of Disease markers · 2024
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  13. Frontiers in genetics · 2022
    Article
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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

12 authors at 7 institutions in 4 countries.

Saleh KhawaledLautenberg Center for Immunology and Cancer Research, Hebrew University-Hadassah Medical School, IMRIC, Jerusalem, Israel.
Giovanni Nigita *Department of Cancer Biology and Genetics, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-8880-4334
Rosario Distefano *Department of Cancer Biology and Genetics, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-7241-7751
Sara OsterLautenberg Center for Immunology and Cancer Research, Hebrew University-Hadassah Medical School, IMRIC, Jerusalem, Israel.
Sung-Suk SuhDepartment of Bioscience, Mokpo National University, Muan, Republic of Korea.
Yoav SmithGenomic Data Analysis Unit, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Abed KhalailehDepartment of Surgery, Hadassah Medical Center, Jerusalem, Israel.
Yong PengDepartment of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, 610041, Chengdu, China.ORCID http://orcid.org/0000-0002-1181-3467
Carlo M CroceDepartment of Cancer Biology and Genetics, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Tamar GeigerDepartment of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Victoria L SeewaldtDepartment of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Rami I AqeilanLautenberg Center for Immunology and Cancer Research, Hebrew University-Hadassah Medical School, IMRIC, Jerusalem, Israel. ramiaq@mail.huji.ac.il.ORCID http://orcid.org/0000-0002-6034-023X
Hebrew University of Jerusalem · ILThe Ohio State University Wexner Medical Center · USCity of Hope · USHadassah Medical Center · ILMokpo National University · KRSichuan University · CNTel Aviv University · IL

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3M
Cancer Gene Discovery to Identify Targetable TargetsR35CA197706 · NCI · OHIO STATE UNIVERSITY · PI CROCE, CARLO M · 2015 to 2021
$6.4M
NCI NIH HHS P30 CA033572NCI NIH HHS R35 CA197706
6 · The paper itself

Abstract

Tumor progression and metastasis are the major causes of death among cancer associated mortality. Metastatic cells acquire features of migration and invasion and usually undergo epithelia-mesenchymal transition (EMT). Acquirement of these various hallmarks rely on different cellular pathways, including TGF-β and Wnt signaling. Recently, we reported that WW domain-containing oxidoreductase (WWOX) acts as a tumor suppressor and has anti-metastatic activities involving regulation of several key microRNAs (miRNAs) in triple-negative breast cancer (TNBC). Here, we report that WWOX restoration in highly metastatic MDA-MB435S cancer cells alters mRNA expression profiles; further, WWOX interacts with various proteins to exert its tumor suppressor function. Careful alignment and analysis of gene and miRNA expression in these cells revealed profound changes in cellular pathways mediating adhesion, invasion and motility. We further demonstrate that WWOX, through regulation of miR-146a levels, regulates SMAD3, which is a member of the TGF-β signaling pathway. Moreover, proteomic analysis of WWOX partners revealed regulation of the Wnt-signaling activation through physical interaction with Disheveled. Altogether, these findings underscore a significant role for WWOX in antagonizing metastasis, further highlighting its role and therapeutic potential in suppressing tumor progression.

Indexed as

Cell MovementCell ProliferationDishevelled ProteinsEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticGenetic PleiotropyHumansMicroRNAsNeoplasm MetastasisProtein Interaction MapsSignal TransductionSmad3 ProteinTransforming Growth Factor betaTriple Negative Breast NeoplasmsTumor Suppressor ProteinsDishevelled ProteinsDVL1 protein, humanMicroRNAsMIRN146 microRNA, humanSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor betaTumor Suppressor ProteinsWW Domain-Containing OxidoreductaseWWOX protein, human

Identifiers

PMID32300104
PMCPMC7162874
OpenAlexW3016533621

What OpenQuestion holds

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LicenceCC BY
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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.