Evidence map›Paper›PMID 37670785›Full record

ArticleiScience2023

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer.

Ahmed H Ghobashi, Truc T Vuong, Jane W Kimani, Christopher A Ladaika, Peter C Hollenhorst, Heather M O'Hagan

Open access · goldAbstract read
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. Observational
  4. Article
  5. Review
  6. Post-translational modifications in CD8Frontiers in immunology · 2026
    Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Advanced biomedical research · 2025
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. A Protective Role of Canonical Wnt/Mediators of inflammation · 2024
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Ahmed H GhobashiGenome, Cell, and Developmental Biology Graduate Program, Department of Biology, Indiana University Bloomington, Bloomington, IN 47405, USA.
Truc T VuongMedical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA.
Jane W KimaniMedical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA.
Christopher A LadaikaGenome, Cell, and Developmental Biology Graduate Program, Department of Biology, Indiana University Bloomington, Bloomington, IN 47405, USA.
Peter C HollenhorstMedical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA.
Heather M O'HaganMedical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA.
Indiana University Bloomington · USIndiana University Health · US

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Sara K Quinney · 1999 to 2026
$59.3M
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Pathology CoreP50CA254897 · NCI · CORIELL INSTITUTE FOR MEDICAL RESEARCH · PI ISSA, JEAN-PIERRE J. · 2021 to 2025
$11.9M
NCATS NIH HHS UL1 TR002529NCI NIH HHS P30 CA082709NCI NIH HHS P50 CA254897
6 · The paper itself

Abstract

Colorectal cancer (CRC) develops in part through the deregulation of different signaling pathways, including activation of the WNT/β-catenin and PI3K/AKT pathways. Additionally, the lysine methyltransferase enhancer of zeste homologue 2 (EZH2) is commonly overexpressed in CRC. EZH2 canonically represses gene transcription by trimethylating lysine 27 of histone H3, but also has non-histone substrates. Here, we demonstrated that in CRC, active AKT phosphorylated EZH2 on serine 21. Phosphorylation of EZH2 by AKT induced EZH2 to interact with and methylate β-catenin at lysine 49, which increased β-catenin's binding to the chromatin. Additionally, EZH2-mediated β-catenin trimethylation induced β-catenin to interact with TCF1 and RNA polymerase II and resulted in dramatic gains in genomic regions with β-catenin occupancy. EZH2 catalytic inhibition decreased stemness but increased migratory phenotypes of CRC cells with active AKT. Overall, we demonstrated that EZH2 modulates AKT-induced changes in gene expression through the AKT/EZH2/β-catenin axis in CRC.

Indexed as

CancerEpigeneticsMolecular biology

Identifiers

PMID37670785
PMCPMC10475482
OpenAlexW4385879527

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.