Evidence map›Paper›PMID 31511827›Full record

ArticleAmerican journal of clinical and experimental urology2019

Wntless promotes cellular viability and resistance to enzalutamide in castration-resistant prostate cancer cells.

Alan P Lombard, Chengfei Liu, Cameron M Armstrong, Leandro S D'Abronzo, Wei Lou, Christopher P Evans, Allen C Gao

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

Article in American journal of clinical and experimental urology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-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

13 citing papers in PubMed, 17 citations in OpenAlex.

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  6. The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 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

7 authors at 1 institution in 1 country.

Alan P LombardDepartment of Urologic Surgery, University of California Davis CA, USA.
Chengfei LiuDepartment of Urologic Surgery, University of California Davis CA, USA.
Cameron M ArmstrongDepartment of Urologic Surgery, University of California Davis CA, USA.
Leandro S D'AbronzoDepartment of Urologic Surgery, University of California Davis CA, USA.
Wei LouDepartment of Urologic Surgery, University of California Davis CA, USA.
Christopher P EvansDepartment of Urologic Surgery, University of California Davis CA, USA.
Allen C GaoDepartment of Urologic Surgery, University of California Davis CA, USA.
University of California, Davis · US

Funding

Targeting AR variants in advanced prostate cancerR01CA225836 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GAO, ALLEN C. · 2019 to 2023
$1.8M
Novel roles of microRNA in androgen receptor signalingR01CA168601 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GAO, ALLEN C. · 2013 to 2017
$1.5M
(PQD-1) NF-kB activation and enzalutamide therapy in metastatic castration resistR21CA179970 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GAO, ALLEN C. · 2013 to 2014
$363k
BLRD VA I01 BX002653NCI NIH HHS R01 CA168601NCI NIH HHS R01 CA225836NCI NIH HHS R21 CA179970
6 · The paper itself

Abstract

backgroundDe-regulation of Wnt signaling pathways has been shown to be associated with progression of castration-resistant prostate cancer and more recently, studies indicate that both canonical and non-canonical Wnt pathways may mediate resistance to anti-androgen therapies such as enzalutamide. However, the mechanisms by which Wnt signaling is altered in prostate cancer remain poorly understood. Wnt pathway function begins with Wnt biogenesis and secretion from Wnt signal sending cells. While previous studies have investigated downstream mechanisms of Wnt pathway alterations in prostate cancer, little is known on the role of Wnt secretion mediating proteins. Wntless (WLS) is thought to be essential for the secretion of all Wnts. In this study, we sought to understand the role of WLS in prostate cancer.

methodsRNA-seq and gene set enrichment analysis were used to understand expression profile changes in enzalutamide-resistant C4-2B-MDVR (MDVR) cells versus parental C4-2B cells. Quantitative-PCR and western blot were used to confirm RNA-seq data and to assess expression changes of gene targets of interest. Rv1 cells were used as a separate model of enzalutamide-resistant prostate cancer. RNAi was used to inhibit WLS expression. Cell viability, colony formation, and PSA ELISA assays were used to assess cell growth and survival.

resultsTranscriptomic profiling revealed enriched Wnt pathway signatures in MDVR versus parental C4-2B cells. We further show that MDVR cells upregulate Wnt signaling and overexpress WLS. Inhibition of WLS decreases Wnt signaling, markedly attenuates prostate cancer cell viability, induces apoptosis, and re-sensitizes enzalutamide-resistant cells to enzalutamide treatment. Lastly, we show that inhibition of WLS reduces AR and AR-variants expression and downstream signaling.

conclusionsOur findings support a role for WLS in the progression of prostate cancer to a treatment-resistant state. Further efforts to understand Wnt signaling pathway alterations in this disease may lead to the development of novel treatments.

Indexed as

castration-resistant prostate cancerenzalutamide resistanceporcnporcupinewlswntlessWnt signaling

Identifiers

PMID31511827
PMCPMC6734040
OpenAlexW2983180216

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.