Evidence map›Paper›PMID 32103169›Full record

ArticleOncogene2020

Commonly observed RNF43 mutations retain functionality in attenuating Wnt/β-catenin signaling and unlikely confer Wnt-dependency onto colorectal cancers.

Shan Li, Marla Lavrijsen, Aron Bakker, Marcin Magierowski, Katarzyna Magierowska, Pengyu Liu, Wenhui Wang, Maikel P Peppelenbosch, Ron Smits

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
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  5. BRAFiScience · 2025
    Article
  6. Article
  7. Article
  8. New Target(s) for RNF43 Regulation: Implications for Therapeutic Strategies.International journal of molecular sciences · 2024
    Review
  9. New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis.In vitro cellular & developmental biology. Animal · 2024
    Review
  10. Article
  11. Clinical and molecular characteristics ofTherapeutic advances in medical oncology · 2024
    Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
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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

9 authors at 4 institutions in 3 countries.

Shan LiDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-4446-2218
Marla LavrijsenDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Aron BakkerDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Marcin MagierowskiDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Katarzyna MagierowskaDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Pengyu LiuDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Wenhui WangDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Maikel P PeppelenboschDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0001-9112-6028
Ron SmitsDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands. m.j.m.smits@erasmusmc.nl.ORCID http://orcid.org/0000-0001-6798-3206
Erasmus MC · NLJagiellonian University · PLArmy Medical University · CNChina Pharmaceutical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer-associated RNF43 mutations lead to activation of β-catenin signaling through aberrantly increasing Wnt-receptor levels at the membrane. Importantly, inactivating RNF43 mutations have been suggested to render cancer cells sensitive to Wnt-based therapeutics. However, the extent to which RNF43 mutations lead to impaired regulation of Wnt/β-catenin signaling has been poorly investigated. Here, we observed that tumors with a functional mismatch repair system show a predominant 5'-location of truncating RNF43 mutations, suggesting C-terminal truncations such as the most commonly reported p.G659fs mutation, do not affect β-catenin signaling. In accordance, expressing C-terminal truncation mutants and wild-type RNF43, showed equal effects on β-catenin signaling, Wnt-receptor turnover, and DVL-binding. We confirmed these observations at endogenous levels by CRISPR-Cas9-mediated knockout of G659fs RNF43 expression in KM12 cells and generating comparable mutations in HEK293T cells. We could not confirm previous reports linking RNF43 to p53 and E-cadherin breakdown. Our data also suggest that only colorectal cancer cells harboring N-terminal mutations of RNF43 convey Wnt-dependency onto the tumor cells. Results of this study have potentially important clinical implications indicating that Wnt-based therapeutics should be applied cautiously in cancer patients harboring RNF43 mutations.

Indexed as

Colorectal NeoplasmsMutationNeoplasm ProteinsUbiquitin-Protein LigasesA549 CellsCaco-2 CellsHCT116 CellsHEK293 CellsHumansProtein DomainsWnt Signaling PathwayNeoplasm ProteinsRNF43 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID32103169
OpenAlexW3007334074

What OpenQuestion holds

Textmetadata
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.