Evidence map›Paper›PMID 21305538›Full record

ArticleCancer2011

Dysfunctional transforming growth factor-β signaling with constitutively active Notch signaling in Barrett's esophageal adenocarcinoma.

Jonathan Mendelson, Shumei Song, Ying Li, Dipen M Maru, Bibhuti Mishra, Marta Davila, Wayne L Hofstetter, Lopa Mishra

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

Article in Cancer, 2011. 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
2.8field-weighted citation impact, top 9% 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, 53 citations in OpenAlex.

  1. Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2017
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  19. Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett's esophagus.Laboratory investigation; a journal of technical methods and pathology · 2016
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Jonathan MendelsonSchool of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Shumei Song
Ying Li
Dipen M Maru
Bibhuti Mishra
Marta Davila
Wayne L Hofstetter
Lopa Mishra
The University of Texas MD Anderson Cancer Center · USGeorge Washington University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Targeting CDK4 in TGS-B Inactivated Gastrointestinal CancersP01CA130821 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MISHRA, LOPA · 2008 to 2013
$6.9M
METASTATIC POTENTIAL OF HUMAN COLORECTAL CARCINOMAR01CA042857 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MISHRA, LOPA · 1986 to 2010
$3.2M
TLR4 and TGF-beta interactions in HCC induced by HCV and alcoholRC2AA019392 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TSUKAMOTO, HIDEKAZU · 2009 to 2010
$1.9M
Gastrointestinal Cell Proliferation and Cell CycleR01CA106614 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MISHRA, LOPA · 2005 to 2009
$1.5M
NCI NIH HHS P01 CA130821NCI NIH HHS P01-CA130821NCI NIH HHS R01 CA042857NCI NIH HHS R01-CA042857NCI NIH HHS R01 CA106614NCI NIH HHS R01-CA106614NIAAA NIH HHS RC2-AA019392NIDDK NIH HHS R01-DK58637
6 · The paper itself

Abstract

backgroundEsophageal adenocarcinoma is often considered to arise from a clonal stem-like population of cells, which is potentially responsible for its poor prognosis. Transforming growth factor β (TGF-β) and Notch signaling pathways play important roles in regulating self-renewal of stem cells and cell-fate determination. Both pathways are frequently implicated in gastrointestinal carcinogenesis. However, their contributions to esophageal adenocarcinoma remain unclear.

methodsWe evaluated TGF-β and Notch signaling components in normal esophagus, Barrett's esophagus, and adenocarcinoma tissues and cell lines via immunohistochemical analysis and immunoblotting; Hes-1 transcription was assayed using a Hes-1 luciferase reporter.

resultsWe observed loss of Smad4 (P<.05) and β2 spectrin (β2SP) (P<.01) in 5/10 Barrett's esophagus and 17/22 adenocarcinoma tissue sections. Concomitantly, dramatically raised levels of Notch signaling components Hes1 and Jagged1 occurred in adenocarcinoma tissues and cell lines compared with normal tissues. In normal esophagus, Oct3/4-positive cells are located in the basal layer (2-3 per cluster), representing a pool of progenitor cells. We observed an expansion of this pool of Oct3/4 positive cells in esophageal adenocarcinoma (15 per cluster). Furthermore, a panel of SOXs proteins documented for stem cell markers exhibit increased expression in tumor cells, indicating expansion of putative cancer stem cells. Finally, we observed growth inhibition in BE3 cells with a γ-secretase inhibitor, but not in SKGT-4 cells. Unlike SKGT-4 cells, BE3 cells have activated Notch signaling with disruption of TGF-β signaling.

conclusionsOur findings demonstrated a potential therapeutic value for targeted therapy in esophageal adenocarcinoma in the setting of loss of β2SP/TGF-β with concomitant constitutively active Notch signaling.

Indexed as

AdenocarcinomaBarrett EsophagusBasic Helix-Loop-Helix ProteinsCalcium-Binding ProteinsCell Line, TumorCell ProliferationCore Binding Factor Alpha 3 SubunitCyclin-Dependent Kinase 4Esophageal NeoplasmsEsophagusHomeodomain ProteinsHumansIntercellular Signaling Peptides and ProteinsJagged-1 ProteinMembrane ProteinsOctamer Transcription Factor-3Basic Helix-Loop-Helix ProteinsCalcium-Binding ProteinsCore Binding Factor Alpha 3 SubunitCyclin-Dependent Kinase 4HES1 protein, humanHomeodomain ProteinsIntercellular Signaling Peptides and ProteinsJAG1 protein, humanJagged-1 ProteinMembrane ProteinsOctamer Transcription Factor-3POU5F1 protein, humanReceptors, NotchRunx3 protein, humanSerrate-Jagged ProteinsTranscription Factor HES-1Transforming Growth Factor beta

Identifiers

PMID21305538
PMCPMC3236645
OpenAlexW1994129770

What OpenQuestion holds

Textmetadata
LicenceTDM
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.