Evidence map›Paper›PMID 27199173›Full record

ArticleScientific reports2016

A Small Molecule Inhibitor of PDK1/PLCγ1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion.

Claudio Raimondi, Veronique Calleja, Riccardo Ferro, Alessandro Fantin, Andrew M Riley, Barry V L Potter, Caroline H Brennan, Tania Maffucci, Banafshé Larijani, Marco Falasca

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

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Phospholipase C.Advances in experimental medicine and biology · 2020
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
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

10 authors at 6 institutions in 3 countries.

Claudio RaimondiQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Inositide Signalling Group, London E1 2AT, UK.
Veronique CallejaCell Biophysics Laboratory, Cancer Research UK, Lincoln's Inn Fields Laboratories, London Research Institute, London WC2A 3LY, UK.
Riccardo FerroQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Inositide Signalling Group, London E1 2AT, UK.
Alessandro FantinUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
Andrew M RileyWolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
Barry V L PotterWolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
Caroline H BrennanQueen Mary University of London, School of Biological and Chemical Sciences, London E1 4NS, UK.
Tania MaffucciQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Inositide Signalling Group, London E1 2AT, UK.
Banafshé LarijaniCell Biophysics Laboratory, Cancer Research UK, Lincoln's Inn Fields Laboratories, London Research Institute, London WC2A 3LY, UK.
Marco FalascaQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Inositide Signalling Group, London E1 2AT, UK.
Queen Mary University of London · GBThe Honourable Society of Lincoln's Inn · GBCurtin University · AUMansfield University · USUniversity College London · GBUniversity of Bath · GB

Funding

Cancer Research UKProstate Cancer UK PG12-23Wellcome Trust 082837Wellcome Trust 101010
6 · The paper itself

Abstract

Strong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCγ1-dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCγ1 interaction and impair PLCγ1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCγ1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCγ1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCγ1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs.

Indexed as

AnimalsAntineoplastic AgentsBreast NeoplasmsCell LineCell MovementDisease Models, AnimalEnzyme InhibitorsHeterograftsHumansInositol PhosphatesMelanomaNeoplasm TransplantationPhospholipase C gammaProtein BindingProtein MultimerizationProtein Serine-Threonine Kinases2-O-benzylinositol 1,3,4,5,6-pentakisphosphateAntineoplastic AgentsEnzyme InhibitorsInositol PhosphatesPDK1 protein, humanPhospholipase C gammaProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring Kinase

Identifiers

PMID27199173
PMCPMC4873738
OpenAlexW2402375029

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.