ArticleMolecular cancer2014
Divergent effects of muscarinic receptor subtype gene ablation on murine colon tumorigenesis reveals association of M3R and zinc finger protein 277 expression in colon neoplasia.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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
30 citing papers in PubMed, 34 citations in OpenAlex.
- Potential mechanisms of Si-Wu-Tang against esophageal squamous cell carcinoma: A machine learning pharmacological study.Medicine · 2026Article
- Selective modulation of murine intestinal MAmerican journal of physiology. Cell physiology · 2026Article
- Bile Acids Are Potential Negative Allosteric Modulators of M1 Muscarinic Receptors.Biomolecules · 2025Article
- Overexpression of ZNF169 promotes the growth and proliferation of colorectal cancer cells via the upregulation of ANKZF1.Oncology reports · 2024Article
- Cholinergic Mechanisms in Gastrointestinal Neoplasia.International journal of molecular sciences · 2024Review
- Novel Therapeutic Approaches for Colorectal Cancer Treatment.International journal of molecular sciences · 2024Article
- Guanine nucleotide exchange factors and colon neoplasia.Frontiers in cell and developmental biology · 2024Review
- Muscarinic receptor agonist-induced βPix binding to β-catenin promotes colon neoplasia.Scientific reports · 2023Article
- Selective Activation of MCancers · 2023Article
- The Roles of Zinc Finger Proteins in Colorectal Cancer.International journal of molecular sciences · 2023Review
- CHRM3 is a novel prognostic factor of poor prognosis and promotes glioblastoma progression via activation of oncogenic invasive growth factors.Oncology research · 2023Article
- Neurotransmitter signaling: a new frontier in colorectal cancer biology and treatment.Oncogene · 2022Review
- Zinc finger protein 277 is an intestinal transit-amplifying cell marker and colon cancer oncogene.JCI insight · 2022Article
- Nerve Dependence in Colorectal Cancer.Frontiers in cell and developmental biology · 2022Review
- Mechanistic Clues Provided by Concurrent Changes in the Expression of Genes Encoding the MFrontiers in physiology · 2022Article
- Differential Actions of Muscarinic Receptor Subtypes in Gastric, Pancreatic, and Colon Cancer.International journal of molecular sciences · 2021Review
- Article
- Exploiting unique features of the gut-brain interface to combat gastrointestinal cancer.The Journal of clinical investigation · 2021Review
- Sympathetic and parasympathetic innervation in cancer: therapeutic implications.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2021Review
- Overcoming Obstacles to Targeting Muscarinic Receptor Signaling in Colorectal Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundM3 and M1 subtype muscarinic receptors are co-expressed in normal and neoplastic intestinal epithelial cells. In mice, ablating Chrm3, the gene encoding M3R, robustly attenuates intestinal tumor formation. Here we investigated the effects of Chrm1 gene ablation, alone and in combination with Chrm3 ablation.
methodsWe used wild-type, Chrm1-/-, Chrm3-/- and combined Chrm1-/-/Chrm3-/- knockout (dual knockout) mice. Animals were treated with azoxymethane, an intestine-selective carcinogen. After 20 weeks, colon tumors were counted and analyzed histologically and by immunohistochemical staining. Tumor gene expression was analyzed using microarray and results validated by RT-PCR. Key findings were extended by analyzing gene and protein expression in human colon cancers and adjacent normal colon tissue.
resultsAzoxymethane-treated Chrm3-/- mice had fewer and smaller colon tumors than wild-type mice. Reductions in colon tumor number and size were not observed in Chrm1-/- or dual knockout mice. To gain genetic insight into these divergent phenotypes we used an unbiased microarray approach to compare gene expression in tumors from Chrm3-/- to those in wild-type mice. We detected altered expression of 430 genes, validated by quantitative RT-PCR for the top 14 up- and 14 down-regulated genes. Comparing expression of this 28-gene subset in tumors from wild-type, Chrm3-/-, Chrm1-/- and dual knockout mice revealed significantly reduced expression of Zfp277, encoding zinc finger protein 277, in tissue from M3R-deficient and dual knockout mice, and parallel changes in Zfp277 protein expression. Notably, mRNA and protein for ZNF277, the human analogue of Zfp277, were increased in human colon cancer compared to adjacent normal colon, along with parallel changes in expression of M3R.
conclusionsOur results identify a novel candidate mouse gene, Zfp277, whose expression pattern is compatible with a role in mediating divergent effects of Chrm3 and Chrm1 gene ablation on murine intestinal neoplasia. The biological importance of this observation is strengthened by finding increased expression of ZNF277 in human colon cancer with a parallel increase in M3R expression. The role of zinc finger protein 277 in colon cancer and its relationship to M3R expression and activation are worthy of further investigation.
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.