Evidence map›Paper›PMID 35675421›Full record

ArticleCancer research2022

Cyclocreatine Suppresses Creatine Metabolism and Impairs Prostate Cancer Progression.

Rachana Patel, Catriona A Ford, Lisa Rodgers, Linda K Rushworth, Janis Fleming, Ernest Mui, Tong Zhang, David Watson, Victoria Lynch, Gillian Mackay and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Article
  3. Creatine kinase regulates energy metabolism and growth of trophoblasts.bioRxiv : the preprint server for biology · 2026
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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

14 authors at 3 institutions in 1 country.

Rachana Patel *CRUK Beatson Institute, Glasgow, United Kingdom.
Catriona A Ford *CRUK Beatson Institute, Glasgow, United Kingdom.
Lisa RodgersCRUK Beatson Institute, Glasgow, United Kingdom.
Linda K RushworthCRUK Beatson Institute, Glasgow, United Kingdom.
Janis FlemingCRUK Beatson Institute, Glasgow, United Kingdom.
Ernest MuiCRUK Beatson Institute, Glasgow, United Kingdom.
Tong ZhangStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
David WatsonStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.ORCID 0000-0003-1094-7604
Victoria LynchDepartment of Histopathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
Gillian MackayCRUK Beatson Institute, Glasgow, United Kingdom.
David SumptonCRUK Beatson Institute, Glasgow, United Kingdom.ORCID 0000-0002-9004-4079
Owen J SansomCRUK Beatson Institute, Glasgow, United Kingdom.ORCID 0000-0001-9540-3010
Johan Vande VoordeCRUK Beatson Institute, Glasgow, United Kingdom.ORCID 0000-0002-7686-0926
Hing Y LeungCRUK Beatson Institute, Glasgow, United Kingdom.ORCID 0000-0002-3933-3975
Cancer Research UK Scotland Institute · GBUniversity of Strathclyde · GBQueen Elizabeth University Hospital · GB

Funding

Cancer Research UK A15151Cancer Research UK A17196Cancer Research UK A21139Cancer Research UK A25045Cancer Research UK A31287
6 · The paper itself

Abstract

Prostate cancer is the second most common cause of cancer mortality in men worldwide. Applying a novel genetically engineered mouse model (GEMM) of aggressive prostate cancer driven by deficiency of the tumor suppressors PTEN and Sprouty2 (SPRY2), we identified enhanced creatine metabolism as a central component of progressive disease. Creatine treatment was associated with enhanced cellular basal respiration in vitro and increased tumor cell proliferation in vivo. Stable isotope tracing revealed that intracellular levels of creatine in prostate cancer cells are predominantly dictated by exogenous availability rather than by de novo synthesis from arginine. Genetic silencing of creatine transporter SLC6A8 depleted intracellular creatine levels and reduced the colony-forming capacity of human prostate cancer cells. Accordingly, in vitro treatment of prostate cancer cells with cyclocreatine, a creatine analog, dramatically reduced intracellular levels of creatine and its derivatives phosphocreatine and creatinine and suppressed proliferation. Supplementation with cyclocreatine impaired cancer progression in the PTEN- and SPRY2-deficient prostate cancer GEMMs and in a xenograft liver metastasis model. Collectively, these results identify a metabolic vulnerability in prostate cancer and demonstrate a rational therapeutic strategy to exploit this vulnerability to impede tumor progression. SIGNIFICANCE: Enhanced creatine uptake drives prostate cancer progression and confers a metabolic vulnerability to treatment with the creatine analog cyclocreatine.

Indexed as

CreatineCreatinineProstatic NeoplasmsAnimalsDisease Models, AnimalHumansIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMicePhosphocreatineCreatineCreatininecyclocreatineIntracellular Signaling Peptides and ProteinsMembrane ProteinsPhosphocreatineSPRY2 protein, human

Identifiers

PMID35675421
PMCPMC9381098
OpenAlexW4282924424

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.