Evidence map›Paper›PMID 27323825›Full record

ArticleOncotarget2016

Secreted HMGB1 from Wnt activated intestinal cells is required to maintain a crypt progenitor phenotype.

Karen R Reed, Fei Song, Maddy A Young, Nurudeen Hassan, Daniel J Antoine, Nesibe-Princess B Gemici, Alan R Clarke, John R Jenkins

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 26% 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

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

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses.International journal of molecular sciences · 2024
    Article
  6. Article
  7. Cell death in the gut epithelium and implications for chronic inflammation.Nature reviews. Gastroenterology & hepatology · 2020
    Review
  8. Article
  9. Article
  10. 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 2 institutions in 2 countries.

Karen R ReedEuropean Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, CF24 4HQ, UK.
Fei SongInfrafrontier GmbH, Neuherberg / München, 85764, Germany.
Maddy A YoungEuropean Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, CF24 4HQ, UK.
Nurudeen HassanEuropean Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, CF24 4HQ, UK.
Daniel J AntoineInstitute of Translational Medicine, University of Liverpool, Liverpool, L69 3BX, UK.
Nesibe-Princess B GemiciEuropean Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, CF24 4HQ, UK.
Alan R ClarkeEuropean Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, CF24 4HQ, UK.
John R JenkinsInstitute of Translational Medicine, University of Liverpool, Liverpool, L69 3BX, UK.
Cardiff University · GBUniversity of Liverpool · GB

Funding

Cancer Research UK 15937Wellcome Trust
6 · The paper itself

Abstract

BACKGROUND AND

aimsColorectal cancer (CRC) arises via multiple genetic changes. Mutation of the tumour suppressor gene APC, a key regulator of Wnt signalling, is recognised as a frequent early driving mutation in CRC. We have previously shown that conditional loss of Apc within the murine small intestine (Apcfloxmice) results in acute Wnt signalling activation, altered crypt-villus architecture and many hallmarks of neoplasia. Our transctipomic profiling (Affymetrix Microarrays) and proteomic profiling (iTRAQ-QSTAR) of Apc-deficient intestine inferred the involvement of High Mobility Group Box 1 (Hmgb1) in CRC pathogenesis. Here we assess the contribution of HMGB1 to the crypt progenitor phenotype seen following Apc loss.

resultsElevated HMGB1 was confirmed in intestinal epithelia and serum following conditional loss of Apc. Treatment of Apcflox mice with anti-HMGB1 neutralising antibody significantly reduced many of the crypt progenitor phenotypes associated with Apc loss; proliferation and apoptosis levels were reduced, cell differentiation was restored and the expansion of stem cell marker expression was eradicated.

methodsHmgb1 levels in intestinal epithelia and serum in Apcflox and ApcMin mice were assessed using qRT-PCR, Western blot and ELISA assays. The functional importance of elevated extracellular Hmgb1 was assessed using an anti-HMGB1 neutralising antibody in Apcflox mice.

conclusionsHMGB1 is expressed and secreted from intestinal epithelial cells in response to Wnt signalling activation. This secreted HMGB1 is required to maintain nearly all aspects of the crypt progenitor phenotype observed following Apc loss and add to the body of accumulating evidence indicating that targeting HMGB1 may be a viable novel therapeutic approach.

Indexed as

Stem Cell NicheAnimalsGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, APCHMGB1 ProteinIntestinal MucosaIntestine, SmallMiceMice, TransgenicMicroarray AnalysisPhenotypeStem CellsWnt ProteinsWnt Signaling PathwayHMGB1 ProteinWnt ProteinsApccolorectal cancerHmgb1intestinal stem cellsWnt signalling

Identifiers

PMID27323825
PMCPMC5239505
OpenAlexW2435300612

What OpenQuestion holds

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LicenceCC BY
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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.