Evidence map›Paper›PMID 24931169›Full record

ArticleOncogene2015

Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities.

S Kagawa, M Natsuizaka, K A Whelan, N Facompre, S Naganuma, S Ohashi, H Kinugasa, A M Egloff, D Basu, P A Gimotty and 6 more

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

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.0field-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

48 citing papers in PubMed, 69 citations in OpenAlex.

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  20. Role of Nrf2 in cell senescence regulation.Molecular and cellular biochemistry · 2021
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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

16 authors at 4 institutions in 1 country.

S Kagawa1] Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
M Natsuizaka1] Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA [3] Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
K A Whelan1] Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
N Facompre1] Departments of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA [2] Philadelphia VA Medical Center, Philadelphia, PA, USA.
S Naganuma1] Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA [3] Department of Pathology, Kochi University Medical School, Kochi, Japan.
S Ohashi1] Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA [3] Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
H Kinugasa1] Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA [3] Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
A M EgloffDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
D Basu1] Departments of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA [2] Philadelphia VA Medical Center, Philadelphia, PA, USA.
P A Gimotty1] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA [2] Division of Biostatistics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
A J Klein-SzantoDepartment of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA.
A J Bass1] Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Division of Cellular and Molecular Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
K-K Wong1] Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Division of Cellular and Molecular Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
J A Diehl1] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA [2] Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA.
A K Rustgi1] Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA [3] Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
H Nakagawa1] Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
University of Pennsylvania · USHarvard University · USFox Chase Cancer Center · USUniversity of Pittsburgh · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 1997 to 2026
$32.5M
Transformed Esophageal Epithelial Cells and the Tumor MicroenvironmentP01CA098101 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUSTGI, ANIL K · 2003 to 2023
$31.7M
Inflammation and the esophageal tumor microenvironmentU01CA143056 · NCI · UNIVERSITY OF PENNSYLVANIA · PI MAHMOOD, UMAR, RUSTGI, ANIL K · 2009 to 2013
$3.1M
The molecular regulation of IGFBP-3 in esophageal epthelial cellsR01DK077005 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI NAKAGAWA, HIROSHI · 2007 to 2011
$1.3M
Targeting mesenchymal-like cells in oral cancer to overcome cetuximab resistanceK08DE022842 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BASU, DEVRAJ · 2012 to 2016
$669k
Genomic and Proteomic Biomarkers for Head and Neck Cancer Risk and PrognosisK07CA137140 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI EGLOFF, ANN MARIE · 2009 to 2013
$519k
A quiescent G0-like cell state as a barrier to eradication oral cancer stem cellsR21DE024396 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BASU, DEVRAJ, NAKAGAWA, HIROSHI · 2014 to 2015
$453k
Integrative mouse pathobiology: GI epithelial biology and geneticsK26OD011179 · OD · UNIVERSITY OF PENNSYLVANIA · PI NAKAGAWA, HIROSHI · 2012 to 2015
$402k
Role of Notch 1 signaling in esophageal carcinogenesisF32CA174146 · NCI · UNIVERSITY OF PENNSYLVANIA · PI WHELAN, KELLY A · 2013 to 2015
$118k
Contribution of G0-like Cells to Maintenance of the Oral Cancer Stem Cell PoolF32DE024685 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI FACOMPRE, NICOLE D. · 2014 to 2015
$96k
Integrative mouse pathobiology: GI epithelial biology and geneticsK26RR032714 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI NAKAGAWA, HIROSHI · 2011 to 2011
$87k
NCI NIH HHS F31 CA174176NCI NIH HHS F32 CA174146NCI NIH HHS F32-CA174176NCI NIH HHS K07 CA137140NCI NIH HHS K07CA137140NCI NIH HHS P01 CA098101NCI NIH HHS P01CA098101NCI NIH HHS P30 CA016520NCI NIH HHS U01 CA143056NCI NIH HHS U01CA143056NCRR NIH HHS K26 RR032714NIDCR NIH HHS F32-DE024685NIDCR NIH HHS K08 DE022842NIDCR NIH HHS K08DE022842NIDCR NIH HHS R21 DE024396NIDDK NIH HHS P30 DK050306NIDDK NIH HHS P30-DK050306NIDDK NIH HHS R01 DK077005NIDDK NIH HHS R01DK077005NIH HHS K26 OD011179
6 · The paper itself

Abstract

Notch activity regulates tumor biology in a context-dependent and complex manner. Notch may act as an oncogene or a tumor-suppressor gene even within the same tumor type. Recently, Notch signaling has been implicated in cellular senescence. Yet, it remains unclear as to how cellular senescence checkpoint functions may interact with Notch-mediated oncogenic and tumor-suppressor activities. Herein, we used genetically engineered human esophageal keratinocytes and esophageal squamous cell carcinoma cells to delineate the functional consequences of Notch activation and inhibition along with pharmacological intervention and RNA interference experiments. When expressed in a tetracycline-inducible manner, the ectopically expressed activated form of Notch1 (ICN1) displayed oncogene-like characteristics inducing cellular senescence corroborated by the induction of G0/G1 cell-cycle arrest, Rb dephosphorylation, flat and enlarged cell morphology and senescence-associated β-galactosidase activity. Notch-induced senescence involves canonical CSL/RBPJ-dependent transcriptional activity and the p16(INK4A)-Rb pathway. Loss of p16(INK4A) or the presence of human papilloma virus (HPV) E6/E7 oncogene products not only prevented ICN1 from inducing senescence but permitted ICN1 to facilitate anchorage-independent colony formation and xenograft tumor growth with increased cell proliferation and reduced squamous-cell differentiation. Moreover, Notch1 appears to mediate replicative senescence as well as transforming growth factor-β-induced cellular senescence in non-transformed cells and that HPV E6/E7 targets Notch1 for inactivation to prevent senescence, revealing a tumor-suppressor attribute of endogenous Notch1. In aggregate, cellular senescence checkpoint functions may influence dichotomous Notch activities in the neoplastic context.

Indexed as

Signal TransductionCarcinoma, Squamous CellCell Cycle CheckpointsCells, CulturedCell Transformation, ViralCellular SenescenceEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaEsophagusHumansKeratinocytesPhosphorylationReceptor, Notch1Retinoblastoma ProteinTransforming Growth Factor betaViral ProteinsNOTCH1 protein, humanReceptor, Notch1Retinoblastoma ProteinTransforming Growth Factor betaViral Proteins

Identifiers

PMID24931169
PMCPMC4268095
OpenAlexW1963891946

What OpenQuestion holds

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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.