Evidence map›Paper›PMID 26930278›Full record

ArticlePloS one2016

Tankyrase Inhibitors Stimulate the Ability of Tankyrases to Bind Axin and Drive Assembly of β-Catenin Degradation-Competent Axin Puncta.

Estefania Martino-Echarri, Mariana G Brocardo, Kate M Mills, Beric R Henderson

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Principles and functions of condensate modifying drugs.Frontiers in molecular biosciences · 2022
    Review
  7. Tankyrase inhibitors hinderParasitology · 2021
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. 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

4 authors at 2 institutions in 1 country.

Estefania Martino-EcharriCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Sydney, Australia.
Mariana G BrocardoCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Sydney, Australia.
Kate M MillsCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Sydney, Australia.
Beric R HendersonCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Sydney, Australia.
University of Sydney · AUWestmead Institute for Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Activation of the wnt signaling pathway is a major cause of colon cancer development. Tankyrase inhibitors (TNKSi) have recently been developed to block the wnt pathway by increasing axin levels to promote degradation of the wnt-regulator β-catenin. TNKSi bind to the PARP (poly(ADP)ribose polymerase) catalytic region of tankyrases (TNKS), preventing the PARylation of TNKS and axin that normally control axin levels through ubiquitination and degradation. TNKSi treatment of APC-mutant SW480 colorectal cancer cells can induce axin puncta which act as sites for assembly of β-catenin degradation complexes, however this process is poorly understood. Using this model system, we found that siRNA knockdown of TNKSs 1 and 2 actually blocked the ability of TNKSi drugs to induce axin puncta, revealing that puncta formation requires both the expression and the inactivation of TNKS. Immunoprecipitation assays showed that treatment of cells with TNKSi caused a strong increase in the formation of axin-TNKS complexes, correlating with an increase in insoluble or aggregated forms of TNKS/axin. The efficacy of TNKSi was antagonized by proteasome inhibitors, which stabilized the PARylated form of TNKS1 and reduced TNKSi-mediated assembly of axin-TNKS complexes and puncta. We hypothesise that TNKSi act to stimulate TNKS oligomerization and assembly of the TNKS-axin scaffold that form puncta. These new insights may help in optimising the future application of TNKSi in anticancer drug design.

Indexed as

AnimalsAntineoplastic AgentsAxin Proteinbeta CateninBlotting, WesternCell Line, TumorColorectal NeoplasmsFluorescent Antibody TechniqueHEK293 CellsHumansMiceTankyrasesWnt Signaling PathwayAntineoplastic AgentsAxin Proteinbeta CateninTankyrasesTNKS2 protein, humanTNKS protein, human

Identifiers

PMID26930278
PMCPMC4773256
OpenAlexW2289501098

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.