Evidence map›Paper›PMID 39752217›Full record

ArticleeLife2025

Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.

Ryosuke Isotani, Masaki Igarashi, Masaomi Miura, Kyoko Naruse, Satoshi Kuranami, Manami Katoh, Seitaro Nomura, Toshimasa Yamauchi

Abstract read
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Emergence of invasiveGut microbes · 2026
    Article
  2. Ghrelin Induces CluInternational journal of molecular sciences · 2026
    Article
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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

8 authors.

Ryosuke IsotaniDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Masaki IgarashiDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-3331-3877
Masaomi MiuraDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kyoko NaruseDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Satoshi KuranamiDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Manami KatohDepartment of Cardiovascular Medicine, The University of Tokyo Graduate, School of Medicine, Tokyo, Japan.
Seitaro NomuraDepartment of Cardiovascular Medicine, The University of Tokyo Graduate, School of Medicine, Tokyo, Japan.
Toshimasa YamauchiDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of murine intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via α7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.

Indexed as

Adaptor Proteins, Signal TransducingNicotineReceptors, NotchSignal TransductionStem CellsYAP-Signaling Proteinsalpha7 Nicotinic Acetylcholine ReceptorAnimalsCarcinogenesisCell Cycle ProteinsCell ProliferationDibenzazepinesHippo Signaling PathwayIntestinesMicePhosphoproteinsAdaptor Proteins, Signal Transducingalpha7 Nicotinic Acetylcholine ReceptorCell Cycle ProteinsdibenzazepineDibenzazepinesNicotinePhosphoproteinsProtein Kinase CProtein Serine-Threonine KinasesReceptors, NotchTrans-ActivatorsTranscription FactorsWwtr1 protein, mouseYap1 protein, mouseYAP-Signaling Proteinsintestinal stem cellmousenAChRnicotineNotchpaneth cellregenerative medicinestem cellsYAP/TAZ

Identifiers

PMID39752217
PMCPMC11698494

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Registered trials

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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.