Evidence map›Paper›PMID 26030909›Full record

ArticlePloS one2015

Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties.

G Bhuvanalakshmi, Frank Arfuso, Michael Millward, Arun Dharmarajan, Sudha Warrier

RetractedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

35 citing papers in PubMed, 71 citations in OpenAlex.

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  13. Drug resistance and combating drug resistance in cancer.Cancer drug resistance (Alhambra, Calif.) · 2019
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

G BhuvanalakshmiDivision of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore, 560 065, India.
Frank ArfusoStem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, 6845, Western Australia; School of Anatomy, Physiology and Human Biology, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia.
Michael MillwardSchool of Medicine and Pharmacology, The University of Western Australia, Crawley, 6009, Western Australia.
Arun DharmarajanStem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, 6845, Western Australia.
Sudha WarrierDivision of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore, 560 065, India; Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, 6845, Western Australia.
Curtin University · AUManipal Academy of Higher Education · INUniversity of Western Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Wnt pathway is integrally involved in regulating self-renewal, proliferation, and maintenance of cancer stem cells (CSCs). We explored the effect of the Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), in modulating epithelial to mesenchymal transition (EMT) in CSCs from human glioblastoma cells lines, U87 and U373. sFRP4 chemo-sensitized CSC-enriched cells to the most commonly used anti-glioblastoma drug, temozolomide (TMZ), by the reversal of EMT. Cell movement, colony formation, and invasion in vitro were suppressed by sFRP4+TMZ treatment, which correlated with the switch of expression of markers from mesenchymal (Twist, Snail, N-cadherin) to epithelial (E-cadherin). sFRP4 treatment elicited activation of the Wnt-Ca2(+) pathway, which antagonizes the Wnt/ß-catenin pathway. Significantly, the chemo-sensitization effect of sFRP4 was correlated with the reduction in the expression of drug resistance markers ABCG2, ABCC2, and ABCC4. The efficacy of sFRP4+TMZ treatment was demonstrated in vivo using nude mice, which showed minimum tumor engraftment using CSCs pretreated with sFRP4+TMZ. These studies indicate that sFRP4 treatment would help to improve response to commonly used chemotherapeutics in gliomas by modulating EMT via the Wnt/ß-catenin pathway. These findings could be exploited for designing better targeted strategies to improve chemo-response and eventually eliminate glioblastoma CSCs.

Indexed as

AnimalsApoptosisATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2CadherinsCell Line, TumorDacarbazineEpithelial-Mesenchymal TransitionGliomaHumansMaleMiceMice, NudeMultidrug Resistance-Associated Protein 2Neoplasm ProteinsABCC2 protein, humanABCC4 protein, humanABCG2 protein, humanATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2CadherinsDacarbazineMultidrug Resistance-Associated Protein 2Neoplasm ProteinsProto-Oncogene ProteinsSecreted Frizzled-Related ProteinsSFRP4 protein, humanTemozolomideTwist-Related Protein 1

Identifiers

PMID26030909
PMCPMC4452329
OpenAlexW1638095649

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.