Evidence map›Paper›PMID 25411317›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Ovarian cancer stem cells express ROR1, which can be targeted for anti-cancer-stem-cell therapy.

Suping Zhang, Bing Cui, Hsien Lai, Grace Liu, Emanuela M Ghia, George F Widhopf, Zhuhong Zhang, Christina C N Wu, Liguang Chen, Rongrong Wu and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% 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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.

  1. Pooled it
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  5. Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026
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62 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

13 authors at 1 institution in 1 country.

Suping ZhangMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Bing CuiMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Hsien LaiMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Grace LiuMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Emanuela M GhiaMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
George F WidhopfMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Zhuhong ZhangMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Christina C N WuMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Liguang ChenMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Rongrong WuMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Richard SchwabMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Dennis A CarsonMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093 tkipps@ucsd.edu dcarson@ucsd.edu.
Thomas J KippsMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093 tkipps@ucsd.edu dcarson@ucsd.edu.
University of California, San Diego · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jing Yang · 1985 to 2026
$124.9M
Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RASSENTI, LAURA Z · 2000 to 2016
$59.5M
NCI NIH HHS P01 CA081534NCI NIH HHS P01-CA081534NCI NIH HHS P30 CA023100NCI NIH HHS P30CA23100
6 · The paper itself

Abstract

Although initially responsive to chemotherapy, many patients with ovarian cancer subsequently develop relapsed and potentially fatal metastatic disease, which is thought to develop from cancer stem cells (CSCs) that are relatively resistant to conventional therapy. Here, we show that CSCs express a type I receptor tyrosine kinase-like orphan receptor (ROR1), which is expressed during embryogenesis and by many different cancers, but not normal postpartum tissues. Ovarian cancers with high levels of ROR1 had stem cell-like gene-expression signatures. Furthermore, patients with ovarian cancers with high levels of ROR1 had higher rates of relapse and a shorter median survival than patients with ovarian cancers that expressed low-to-negligible amounts of ROR1. We found that ROR1-positive (ROR1(+)) cells isolated from primary tumor-derived xenografts (PDXs) also expressed aldehyde dehydrogenase 1 (ALDH1) and had a greater capacity to form spheroids and to engraft immune-deficient mice than did ROR1-negative (ROR1(Neg)) ovarian cancer cells isolated from the same tumor population. Treatment with UC-961, an anti-ROR1 mAb, or shRNA silencing of ROR1 inhibited expression of the polycomb ring-finger oncogene, Bmi-1, and other genes associated with the epithelial-mesenchymal transition. Moreover, shRNA silencing of ROR1, depletion of ROR1(+) cells, or treatment with UC-961 impaired the capacity of ovarian cancer cells to form spheroids or tumor xenografts. More importantly, treatment with anti-ROR1 affected the capacity of the xenograft to reseed a virgin mouse, indicating that targeting ROR1 may affect CSC self-renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which contributes to their capacity to form tumors, making ROR1 a potential target for the therapy of patients with ovarian cancer.

Indexed as

AnimalsAntibodies, MonoclonalCell Line, TumorFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunoblottingKaplan-Meier EstimateMice, Inbred NODMice, KnockoutMice, SCIDMicroscopy, ConfocalMolecular Targeted TherapyNeoplastic Stem CellsOvarian NeoplasmsAntibodies, MonoclonalReceptor Tyrosine Kinase-like Orphan ReceptorsROR1 protein, humanmonoclonal antibodyovarian cancer stem cellPDX mice modelROR1

Identifiers

PMID25411317
PMCPMC4260559
OpenAlexW2092864627

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.