Evidence map›Paper›PMID 38350962›Full record

ArticleCancer & metabolism2024

Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response.

Ceren Yalaz, Esther Bridges, Nasullah K Alham, Christos E Zois, Jianzhou Chen, Karim Bensaad, Ana Miar, Elisabete Pires, Ruth J Muschel, James S O McCullagh and 1 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer & metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Ceren YalazMolecular Oncology Laboratories, Department of Medical Oncology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. cerenyalaz@gmail.com.
Esther BridgesMolecular Oncology Laboratories, Department of Medical Oncology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Nasullah K AlhamDepartment of Engineering Science, Institute of Biomedical Engineering (IBME), University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Christos E ZoisMolecular Oncology Laboratories, Department of Medical Oncology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Jianzhou ChenDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Karim BensaadMolecular Oncology Laboratories, Department of Medical Oncology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Ana MiarDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Elisabete PiresDepartment of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
Ruth J MuschelDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
James S O McCullaghDepartment of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
Adrian L HarrisMolecular Oncology Laboratories, Department of Medical Oncology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
University of Oxford · GBJohn Radcliffe Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPDE6H encodes PDE6γ', the inhibitory subunit of the cGMP-specific phosphodiesterase 6 in cone photoreceptors. Inhibition of PDE6, which has been widely studied for its role in light transduction, increases cGMP levels. The purpose of this study is to characterise the role of PDE6H in cancer cell growth.

methodsFrom an siRNA screen for 487 genes involved in metabolism, PDE6H was identified as a controller of cell cycle progression in HCT116 cells. Role of PDE6H in cancer cell growth and metabolism was studied through the effects of its depletion on levels of cell cycle controllers, mTOR effectors, metabolite levels, and metabolic energy assays. Effect of PDE6H deletion on tumour growth was also studied in a xenograft model.

resultsPDE6H knockout resulted in an increase of intracellular cGMP levels, as well as changes to the levels of nucleotides and key energy metabolism intermediates. PDE6H knockdown induced G1 cell cycle arrest and cell death and reduced mTORC1 signalling in cancer cell lines. Both knockdown and knockout of PDE6H resulted in the suppression of mitochondrial function. HCT116 xenografts revealed that PDE6H deletion, as well as treatment with the PDE5/6 inhibitor sildenafil, slowed down tumour growth and improved survival, while sildenafil treatment did not have an additive effect on slowing the growth of PDE6γ'-deficient tumours.

conclusionsOur results indicate that the changes in cGMP and purine pools, as well as mitochondrial function which is observed upon PDE6γ' depletion, are independent of the PKG pathway. We show that in HCT116, PDE6H deletion replicates many effects of the dark retina response and identify PDE6H as a new target in preventing cancer cell proliferation and tumour growth.

Identifiers

PMID38350962
PMCPMC10863171
OpenAlexW4391785524

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LicenceCC BY
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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.