ReviewCancers2016
Control of Wnt Receptor Turnover by R-spondin-ZNRF3/RNF43 Signaling Module and Its Dysregulation in Cancer.
Review in Cancers, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
103 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Pooled it
- Do all colorectal mucinous adenocarcinomas arise via the serrated neoplasia pathway?The journal of pathology. Clinical research · 2026Article
- Loss of ZNRF3/RNF43 unleashes EGFR in cancer.eLife · 2026Article
- A Targeted R-Spondin Mimetic Induces Hepatocyte-Specific Activation of Wnt Signaling and Cell Proliferation in Mice.Gastro hep advances · 2026Article
- Oral Delivery of R-spondin1-Loaded Small Extracellular Vesicles Activates WNT Signalling Pathway to Accelerate Intestinal Injury Repair and Reverse Ageing.Journal of extracellular vesicles · 2026Article
- Bioinformatic Analysis of RNF43 and Its Co-expressors As Prognostic Biomarkers for Gastric Cancer.Cureus · 2025Article
- FZD7 expression marks mammary tumor-initiating cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Wnt induces FZD5/8 endocytosis and degradation and the involvement of RSPO-ZNRF3/RNF43 and DVL.eLife · 2025Article
- Structural insights into Wnt/β-catenin signaling regulation by LGR4, R-spondin, and ZNRF3.Nature communications · 2025Article
- The impact of an RNA-binding protein group on regulating the RSPO-LGR4/5-ZNRF3/RNF43 module and the immune microenvironment in hepatocellular carcinoma.BMC cancer · 2025Article
- Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels.Oncogene · 2025Article
- 2-Cyanopyrimidine-Containing Molecules for N-Terminal Selective Cyclization of Phage-Displayed Peptides.ACS chemical biology · 2025Article
- Wnt/β-catenin pathway activation is associated with glucocorticoid secretion in adrenocortical carcinoma, but not directly with immune cell infiltration.Frontiers in endocrinology · 2025Article
- MiR-668-5p targets ZNRF3, an E3 ubiquitin ligase to enhance osteoblast function and alleviate senescence in doxorubicin-induced age-related bone loss.Frontiers in endocrinology · 2025Article
- Cushing's Disease Manifestation inInternational journal of molecular sciences · 2024Article
- A phase I dose escalation study of the LRP5 antagonist BI 905681 in patients with advanced and metastatic solid tumors.ESMO open · 2024Article
- A phase I dose-escalation study of LRP5/6 antagonist BI 905677 in patients with advanced solid tumors.ESMO open · 2024Article
- New Target(s) for RNF43 Regulation: Implications for Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?Pharmaceuticals (Basel, Switzerland) · 2024Review
- Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of the Wnt/β-catenin pathway is frequently found in various cancers, often through mutations of downstream components. Inhibiting β-catenin signaling in tumors with downstream pathway mutations remains challenging, due to a lack of favorable targets. On the other hand, targeting upstream components of the Wnt pathway is rather straightforward. However, it is difficult to identify tumors addicted to autocrine or paracrine Wnt signaling. Discovery of the R-spondin-ZNRF3/RNF43 signaling module and its genetic alterations in cancers represents a breakthrough in this area. Membrane E3 ligase ZNRF3 and RNF43 are critical negative feedback regulators of the Wnt pathway, which function through promoting ubiquitination and degradation of Wnt receptors. R-spondin proteins (RSPO1-4) serve as natural antagonists of ZNRF3/RNF43. To maintain strong and sustained Wnt/β-catenin signaling, cancers need to overcome ZNRF3/RNF43-mediated feedback inhibition. Indeed, mutations of RNF43/ZNRF3 and recurrent translocations of RSPO2/RSPO3 have recently been identified in various cancers. Significantly, genetic alterations in RNF43/ZNRF3/RSPO2/RSPO3 have shown promise as predictive biomarkers in pre-clinical models for the efficacy of upstream Wnt inhibitors. In this review, we will discuss the biology of the R-spondin-ZNRF3/RNF43 signaling module, cancer-associated alterations of this signaling module, and their value as biomarkers to identify Wnt-addicted tumors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.