Evidence map›Paper›PMID 31129492›Full record

ArticleNeoplasia (New York, N.Y.)2019

Notch and mTOR Signaling Pathways Promote Human Gastric Cancer Cell Proliferation.

Elise S Hibdon, Nataliya Razumilava, Theresa M Keeley, Gabriela Wong, Sumeet Solanki, Yatrik M Shah, Linda C Samuelson

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

Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 6% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

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  9. Increased Expression ofIranian journal of public health · 2025
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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

7 authors at 1 institution in 1 country.

Elise S HibdonDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109.
Nataliya RazumilavaDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109.
Theresa M KeeleyDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109.
Gabriela WongDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109.
Sumeet SolankiDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109.
Yatrik M ShahDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109.
Linda C SamuelsonDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109. Electronic address: lcsam@umich.edu.
University of Michigan–Ann Arbor · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OMARY, BISHR · 1986 to 2021
$22.5M
Role of Hedgehog Signaling in Chronic Gastritis and MetaplasiaP01DK062041 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MERCHANT, JUANITA L. · 2002 to 2017
$20.6M
Wnt pathway regulation of human gastric stem cell functionK01DK111710 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HIBDON, ELISE · 2017 to 2018
$183k
NIDDK NIH HHS K01 DK111710NIDDK NIH HHS P01 DK062041NIDDK NIH HHS P30 DK034933
6 · The paper itself

Abstract

Notch pathway signaling is known to promote gastric stem cell proliferation, and constitutive pathway activation induces gastric tumors via mTORC1 activation in mouse genetic models. The purpose of this study was to determine whether human gastric adenocarcinomas are similarly dependent on Notch and mTORC1 signaling for growth. Gene expression profiling of 415 human gastric adenocarcinomas in The Cancer Genome Atlas, and a small set of locally obtained gastric cancers showed enhanced expression of Notch pathway components, including Notch ligands, receptors and downstream target genes. Human gastric adenocarcinoma tissues and chemically induced mouse gastric tumors both exhibited heightened Notch and mTORC1 pathway signaling activity, as evidenced by increased expression of the NOTCH1 receptor signaling fragment NICD, the Notch target HES1, and the mTORC1 target phosphorylated S6 ribosomal protein. Pharmacologic inhibition of either Notch or mTORC1 signaling reduced growth of human gastric cancer cell lines, with combined pathway inhibition causing a further reduction in growth, suggesting that both pathways are activated to promote gastric cancer cell proliferation. Further, mTORC1 signaling was reduced after Notch inhibition suggesting that mTOR is downstream of Notch in gastric cancer cells. Analysis of human gastric organoids derived from paired control and gastric cancer tissues also exhibited reduced growth in culture after Notch or mTOR inhibition. Thus, our studies demonstrate that Notch and mTOR signaling pathways are commonly activated in human gastric cancer to promote cellular proliferation. Targeting these pathways in combination might be an effective therapeutic strategy for gastric cancer treatment.

Indexed as

AdenocarcinomaAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMaleMechanistic Target of Rapamycin Complex 1MiceReceptor, Notch1Receptors, NotchSignal TransductionStomach NeoplasmsTOR Serine-Threonine KinasesTranscription Factor HES-1HES1 protein, humanMechanistic Target of Rapamycin Complex 1MTOR protein, humanReceptor, Notch1Receptors, NotchTOR Serine-Threonine KinasesTranscription Factor HES-1

Identifiers

PMID31129492
PMCPMC6536707
OpenAlexW2944972789

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.