Evidence map›Paper›PMID 38740881›Full record

ArticleCancer gene therapy2024

Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer.

Letizia Rinella, Gloria Fiorentino, Mara Compagno, Cristina Grange, Massimo Cedrino, Francesca Marano, Ornella Bosco, Elena Vissio, Luisa Delsedime, Patrizia D'Amelio and 3 more

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Article in Cancer gene therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

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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

13 authors.

Letizia RinellaDepartment of Medical Sciences, University of Turin, Turin, Italy.
Gloria FiorentinoDepartment of Medical Sciences, University of Turin, Turin, Italy.
Mara CompagnoCenter for Experimental Research and Medical Studies (CeRMS), Molinette Hospital, Città della Salute e della Scienza, University of Turin, Turin, Italy.
Cristina GrangeDepartment of Medical Sciences, University of Turin, Turin, Italy.
Massimo CedrinoMolecular Biotechnology Center, University of Turin, Turin, Italy.
Francesca MaranoDepartment of Medical Sciences, University of Turin, Turin, Italy.
Ornella BoscoDepartment of Medical Sciences, University of Turin, Turin, Italy.
Elena VissioUnit of Pathology, Molinette Hospital, Città della Salute e della Scienza, University of Turin, Turin, Italy.
Luisa DelsedimeUnit of Pathology, Molinette Hospital, Città della Salute e della Scienza, University of Turin, Turin, Italy.
Patrizia D'AmelioDepartment of Medical Sciences, University of Turin, Turin, Italy.
Benedetta BussolatiDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Emanuela ArvatDepartment of Medical Sciences, University of Turin, Turin, Italy.
Maria Graziella CatalanoDepartment of Medical Sciences, University of Turin, Turin, Italy. mariagraziella.catalano@unito.it.ORCID 0000-0002-1170-8245

Funding

Fondazione CRT (CRT Foundation) 2020.1694Università degli Studi di Torino (University of Turin) EX-60%
6 · The paper itself

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor prognosis and remains an incurable fatal disease. Therefore, the identification of molecular markers involved in cancer progression is urgently needed to develop more-effective therapies. The present study investigated the role of the Wnt signaling modulator Dickkopf-1 (DKK1) in the growth and metastatic progression of mCRPC. DKK1 silencing through siRNA and deletion via CRISPR/Cas9 editing were performed in two different metastatic castration-resistant prostate cancer cell lines (PC3 and DU145). A xenograft tumor model was used to assess tumor growth and metastases. In in vitro experiments, both DKK1 silencing and deletion reduced cell growth and migration of both cell lines. DKK1 knockout clones (DKK1-KO) exhibited cell cycle arrest, tubulin reorganization, and modulation of tumor metastasis-associated genes. Furthermore, in DKK1-KO cells, E-cadherin re-expression and its membrane co-localization with β-catenin were observed, contributing to reduced migration; Cadherin-11, known to increase during epithelial-mesenchymal transition, was down-regulated in DKK1-KO cells. In the xenograft mouse model, DKK1 deletion not only reduced tumor growth but also inhibited the formation of lung metastases. In conclusion, our findings support the key role of DKK1 in the growth and metastatic dissemination of mCRPC, both in vitro and in vivo.

Indexed as

Cell ProliferationIntercellular Signaling Peptides and ProteinsProstatic Neoplasms, Castration-ResistantAnimalsCell Line, TumorCell MovementEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansMaleMiceNeoplasm MetastasisXenograft Model Antitumor AssaysDKK1 protein, humanIntercellular Signaling Peptides and Proteins

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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.