Evidence map›Paper›PMID 32037952›Full record

ArticleCancer biology & therapy2020

APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.

Erik S Blomain, Jeffrey A Rappaport, Amanda M Pattison, Babar Bashir, Ellen Caparosa, Jonathan Stem, Adam E Snook, Scott A Waldman

Open access · bronzeAbstract read
In one paragraph

Article in Cancer biology & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer.Expert review of precision medicine and drug development · 2021
    Article
  10. Review
  11. 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

8 authors at 1 institution in 1 country.

Erik S BlomainDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.
Jeffrey A RappaportDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.
Amanda M PattisonDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.
Babar BashirDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0002-6843-1179
Ellen CaparosaDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.
Jonathan StemDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.
Adam E SnookDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-9216-4560
Scott A WaldmanDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.
Thomas Jefferson University · US

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI Andrew Chapman · 1995 to 2026
$94.8M
CLINICAL PHARMACOLOGY TRAINING PROGRAMT32GM008562 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI WALTER K KRAFT, Scott A. Waldman · 1995 to 2026
$10.2M
Guanylin GUCY2C axis in Colorectal Cancer InitiationR01CA204481 · NCI · THOMAS JEFFERSON UNIVERSITY · PI WALDMAN, SCOTT A · 2017 to 2021
$1.8M
(PQ1) GUCY2C hormone loss translates APC-Beta-catenin mutations into epithelial transformationR01CA206026 · NCI · THOMAS JEFFERSON UNIVERSITY · PI WALDMAN, SCOTT A · 2016 to 2020
$1.8M
Restoring Guanylin-Guanylate cyclase C Signaling to Prevent Colorectal CancerF30CA232469 · NCI · THOMAS JEFFERSON UNIVERSITY · PI RAPPAPORT, JEFFREY · 2018 to 2022
$188k
GUCY2C hormone suppression links obesity with colorectal cancerF30CA180500 · NCI · THOMAS JEFFERSON UNIVERSITY · PI BLOMAIN, ERIK · 2013 to 2015
$130k
Reactivating the GUCY2C signaling axis opposes oncogenic B-catenin for cancer chemopreventionF31CA225123 · NCI · THOMAS JEFFERSON UNIVERSITY · PI PATTISON, AMANDA · 2018 to 2020
$112k
NCI NIH HHS F30 CA180500NCI NIH HHS F30 CA232469NCI NIH HHS F31 CA225123NCI NIH HHS P30 CA056036NCI NIH HHS R01 CA204481NCI NIH HHS R01 CA206026NIGMS NIH HHS T32 GM008562
6 · The paper itself

Abstract

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation eliminates guanylin expression at tumor initiation, silencing GUCY2C signaling which, in turn, dysregulates intestinal homeostatic mechanisms contributing to tumor progression. They expand the mechanistic paradigm for colorectal cancer from a disease of irreversible mutations in APC and β-catenin to one of guanylin hormone loss whose replacement, and reconstitution of GUCY2C signaling, could prevent tumorigenesis.

Indexed as

Adenomatous Polyposis Coli ProteinAnimalsbeta CateninCell Line, TumorColorectal NeoplasmsDatabases, GeneticGastrointestinal HormonesGenes, Tumor SuppressorHumansIntestinal MucosaMiceMice, KnockoutNatriuretic PeptidesParacrine CommunicationReceptors, EnterotoxinSignal TransductionAdenomatous Polyposis Coli Proteinadenomatous polyposis coli protein, mouseAPC protein, humanbeta CateninGastrointestinal HormonesguanylinGUCY2C protein, humanNatriuretic PeptidesReceptors, EnterotoxinTCF Transcription Factorschemopreventioncolorectal cancerguanylyl cyclase CGUCA2Atranscriptional regulation

Identifiers

PMID32037952
PMCPMC7515458
OpenAlexW3005938678

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.