Evidence map›Paper›PMID 31752944›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

Downregulation of class II phosphoinositide 3-kinase PI3K-C2β delays cell division and potentiates the effect of docetaxel on cancer cell growth.

Ouma Cisse, Muzthahid Quraishi, Federico Gulluni, Federica Guffanti, Ioanna Mavrommati, Methushaa Suthanthirakumaran, Lara C R Oh, Jessica N Schlatter, Ambisha Sarvananthan, Massimo Broggini and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 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
1.1field-weighted citation impact, top 22% 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, 23 citations in OpenAlex.

  1. Article
  2. Review
  3. Targeting PI3K/Akt signaling in prostate cancer therapy.Journal of cell communication and signaling · 2023
    Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. An Overview of Class II Phosphoinositide 3-Kinases.Current topics in microbiology and immunology · 2022
    Article
  9. Review
  10. Article
  11. Article
  12. PI3K inhibitors in thrombosis and cardiovascular disease.Clinical and translational medicine · 2020
    Review
  13. Article
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 at 5 institutions in 3 countries.

Ouma CisseQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.
Muzthahid QuraishiQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.
Federico GulluniMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy.
Federica GuffantiLaboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri IRCCS", Milan, Italy.
Ioanna MavrommatiQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.
Methushaa SuthanthirakumaranQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.
Lara C R OhQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.
Jessica N SchlatterQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.
Ambisha SarvananthanQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.
Massimo BrogginiLaboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri IRCCS", Milan, Italy.
Emilio HirschMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy.
Marco FalascaQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.
Tania MaffucciQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK. t.maffucci@qmul.ac.uk.
Queen Mary University of London · GBMario Negri Institute for Pharmacological Research · ITUniversity of Turin · ITCurtin University · AUInstitute of Cancer Research · GB

Funding

Associazione Italiana per la Ricerca sul Cancro AIRC 21875Fondazione Italiana per la Ricerca sul Cancro FIRC 19421Prostate Cancer UK PG13-029
6 · The paper itself

Abstract

backgroundAlteration of signalling pathways regulating cell cycle progression is a common feature of cancer cells. Several drugs targeting distinct phases of the cell cycle have been developed but the inability of many of them to discriminate between normal and cancer cells has strongly limited their clinical potential because of their reduced efficacy at the concentrations used to limit adverse side effects. Mechanisms of resistance have also been described, further affecting their efficacy. Identification of novel targets that can potentiate the effect of these drugs or overcome drug resistance can provide a useful strategy to exploit the anti-cancer properties of these agents to their fullest.

methodsThe class II PI3K isoform PI3K-C2β was downregulated in prostate cancer PC3 cells and cervical cancer HeLa cells using selective siRNAs and the effect on cell growth was determined in the absence or presence of the microtubule-stabilizing agent/anti-cancer drug docetaxel. Mitosis progression was monitored by time-lapse microscopy. Clonogenic assays were performed to determine the ability of PC3 and HeLa cells to form colonies upon PI3K-C2β downregulation in the absence or presence of docetaxel. Cell multi-nucleation was assessed by immunofluorescence. Tumour growth in vivo was assessed using a xenograft model of PC3 cells upon PI3K-C2β downregulation and in combination with docetaxel.

resultsDownregulation of PI3K-C2β delays mitosis progression in PC3 and HeLa cells, resulting in reduced ability to form colonies in clonogenic assays in vitro. Compared to control cells, PC3 cells lacking PI3K-C2β form smaller and more compact colonies in vitro and they form tumours more slowly in vivo in the first weeks after cells implant. Stable and transient PI3K-C2β downregulation potentiates the effect of low concentrations of docetaxel on cancer cell growth. Combination of PI3K-C2β downregulation and docetaxel almost completely prevents colonies formation in clonogenic assays in vitro and strongly inhibits tumour growth in vivo.

conclusionsThese data reveal a novel role for the class II PI3K PI3K-C2β during mitosis progression. Furthermore, data indicate that blockade of PI3K-C2β might represent a novel strategy to potentiate the effect of docetaxel on cancer cell growth.

Indexed as

AnimalsAntineoplastic AgentsCell DivisionCell ProliferationClass II Phosphatidylinositol 3-KinasesDocetaxelDown-RegulationFemaleHeLa CellsHumansMaleMice, NudePC-3 CellsProstatic NeoplasmsRandom AllocationTransfectionAntineoplastic AgentsClass II Phosphatidylinositol 3-KinasesDocetaxelPIK3C2B protein, humanDocetaxelMitosisPhosphoinositide 3-kinasePI3K-C2βProstate cancer

Identifiers

PMID31752944
PMCPMC6873561
OpenAlexW2991537963

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.