Evidence map›Paper›PMID 34465361›Full record

ArticleJournal of experimental & clinical cancer research : CR2021

SHOX2 cooperates with STAT3 to promote breast cancer metastasis through the transcriptional activation of WASF3.

Yong Teng, Reid Loveless, Elayne M Benson, Li Sun, Austin Y Shull, Chloe Shay

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 7% 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, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
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  16. siRNA and targeted delivery systems in breast cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    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

6 authors at 3 institutions in 1 country.

Yong TengDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, 201 Dowman Dr, GA, 30322, Atlanta, USA. yong.teng@emory.edu.
Reid LovelessDepartment of Oral Biology and Diagnostic Sciences, Georgia Cancer Center, Augusta University, 30912, Augusta, GA, USA.
Elayne M BensonDepartment of Biology, Presbyterian College, 29325, Clinton, SC, USA.
Li SunDepartment of Oral Biology and Diagnostic Sciences, Georgia Cancer Center, Augusta University, 30912, Augusta, GA, USA.
Austin Y ShullDepartment of Biology, Presbyterian College, 29325, Clinton, SC, USA.
Chloe ShayEmory Children's Center, Emory University School of Medicine, 30322, Atlanta, GA, USA.
Augusta University Health · USEmory University · USPresbyterian College · US

Funding

South Carolina IDeA Networks of Biomedical Research (SC INBRE V)P20GM103499 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI EDIE C GOLDSMITH · 2012 to 2026
$61.0M
ATAD3A as a Novel Target in Head and Neck CancerR01DE028351 · NIDCR · EMORY UNIVERSITY · PI TENG, YONG · 2019 to 2023
$1.9M
The Impact of Arf1 on Hypoxia Signaling and Oral CancerR03DE028387 · NIDCR · EMORY UNIVERSITY · PI TENG, YONG · 2019 to 2020
$306k
NIDCR NIH HHS R01 DE028351NIDCR NIH HHS R01DE028351NIDCR NIH HHS R03 DE028387NIDCR NIH HHS R03DE028387NIGMS NIH HHS P20 GM103499NIGMS NIH HHS P20GM103499-20
6 · The paper itself

Abstract

backgroundMetastasis is most often the root cause of cancer-related death. Human short stature homeobox 2 (SHOX2), a homeodomain transcription factor, is a novel inducer of epithelial-to-mesenchymal transition in breast cancer cells, though its exact role and underlying mechanisms in metastasis are not well understood.

methodsTCGA analysis was performed to identify the clinical relevance of SHOX2 in breast cancer. Gene depletion was achieved by short hairpin RNA and small interfering RNA. Molecular regulations and alterations were assessed by Western blotting, immunoprecipitation, immunohistochemistry, qRT-PCR, chromatin immunoprecipitation coupled with qPCR (ChIP-qPCR), and ChIP/re-ChIP. The impact of SHOX2 signaling on tumor growth and metastasis was evaluated in orthotopic breast tumor mice.

resultsThe expression level of SHOX2 is strongly associated with poor distant metastasis-free survival in breast cancer patients and inactivation of SHOX2 suppresses breast tumor growth and metastasis in mice. In breast cancer cells, SHOX2 directly activates Wiskott-Aldridge syndrome protein family member 3 (WASF3), a metastasis-promoting gene, at the transcriptional level, leading to a significant increase in metastatic potential. Mechanistically, SHOX2 activates signal transducer and activator of transcription 3 (STAT3) and recruits it to the WASF3 promoter, where STAT3 cooperates with SHOX2 to form a functional immunocomplex to promote WASF3 transcriptional activity in breast cancer cells. WASF3 knockdown abrogates SHOX2-induced metastasis, but not SHOX2-dependent tumorigenesis.

conclusionsThese findings provide a critical link between the SHOX2-STAT3-WASF3 signaling axis and metastasis and suggest that the targeting of this signaling node may represent a valuable alternative strategy for combating breast cancer metastasis.

Indexed as

Neoplasm MetastasisTranscriptional ActivationAnimalsBreast NeoplasmsCell Line, TumorCell ProliferationFemaleHomeodomain ProteinsHumansMiceMice, Inbred NODPromoter Regions, GeneticProtein BindingSignal TransductionSTAT3 Transcription FactorWiskott-Aldrich Syndrome Protein FamilyHomeodomain ProteinsSHOX2 protein, humanSTAT3 protein, humanSTAT3 Transcription FactorWASF3 protein, humanWiskott-Aldrich Syndrome Protein FamilyBreast cancerMetastasisSHOX2STAT3Transcriptional activationWASF3

Identifiers

PMID34465361
PMCPMC8406721
OpenAlexW3196684755

What OpenQuestion holds

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LicenceCC BY
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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.