Evidence map›Paper›PMID 31434712›Full record

ArticleCancer discovery2019

ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells.

Ana Jimenez-Pascual, James S Hale, Anja Kordowski, Jamie Pugh, Daniel J Silver, Defne Bayik, Gustavo Roversi, Tyler J Alban, Shilpa Rao, Rui Chen and 7 more

Open access · greenAbstract read
In one paragraph

Article in Cancer discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

60 citing papers in PubMed, 83 citations in OpenAlex.

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  6. Sprouty in Tumors of the Nervous System.International journal of molecular sciences · 2025
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  13. Caveolae: Metabolic Platforms at the Crossroads of Health and Disease.International journal of molecular sciences · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 4 countries.

Ana Jimenez-PascualCardiff University School of Biosciences, European Cancer Stem Cell Research Institute, Cardiff, United Kingdom.
James S HaleDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. fas@cardiff.ac.uk lathiaj@ccf.org james.s.hale@case.edu.
Anja KordowskiCardiff University School of Biosciences, European Cancer Stem Cell Research Institute, Cardiff, United Kingdom.
Jamie PughCardiff University School of Biosciences, European Cancer Stem Cell Research Institute, Cardiff, United Kingdom.ORCID 0000-0001-6943-9730
Daniel J SilverDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Defne BayikDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.ORCID 0000-0002-4740-8869
Gustavo RoversiDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Tyler J AlbanDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Shilpa RaoDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Rui ChenDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Thomas M McIntyreDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.ORCID 0000-0001-7802-5900
Giorgio ColomboDepartment of Chemistry, University of Pavia and Institute of Molecular Recognition Chemistry (ICRM-CNR), Milano, Italy.
Giulia TarabolettiIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.ORCID 0000-0001-8780-5001
Karl O HolmbergDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Karin Forsberg-NilssonDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Justin D LathiaDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. fas@cardiff.ac.uk lathiaj@ccf.org james.s.hale@case.edu.
Florian A SiebzehnrublCardiff University School of Biosciences, European Cancer Stem Cell Research Institute, Cardiff, United Kingdom. fas@cardiff.ac.uk lathiaj@ccf.org james.s.hale@case.edu.ORCID 0000-0001-8411-8775
Cleveland Clinic Lerner College of Medicine · USCardiff University · GBScience for Life Laboratory · SEInstitute of Chemistry of Molecular Recognition · ITMario Negri Institute for Pharmacological Research · IT

Funding

RESEARCH ONCOLOGY TRAINING GRANTT32CA059366 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI JACKSON, MARK W. · 1993 to 2025
$5.5M
Dynamic regulation of thrombosis by the platelet proteomeR01HL130090 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS M · 2016 to 2019
$1.6M
Cancer Research UKMedical Research Council MR/S007709/1NCI NIH HHS T32 CA059366NHLBI NIH HHS R01 HL130090
6 · The paper itself

Abstract

Glioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics are preferentially linked to GBM cancer stem cells (GSC), but how GSCs maintain their stemness is incompletely understood and the subject of intense investigation. Here, we identify a novel signaling loop that induces and maintains GSCs consisting of an atypical metalloproteinase, ADAMDEC1, secreted by GSCs. ADAMDEC1 rapidly solubilizes FGF2 to stimulate FGFR1 expressed on GSCs. FGFR1 signaling induces upregulation of ZEB1 via ERK1/2 that regulates ADAMDEC1 expression through miR-203, creating a positive feedback loop. Genetic or pharmacologic targeting of components of this axis attenuates self-renewal and tumor growth. These findings reveal a new signaling axis for GSC maintenance and highlight ADAMDEC1 and FGFR1 as potential therapeutic targets in GBM. SIGNIFICANCE: Cancer stem cells (CSC) drive tumor growth in many cancers including GBM. We identified a novel sheddase, ADAMDEC1, which initiates an FGF autocrine loop to promote stemness in CSCs. This loop can be targeted to reduce GBM growth.

Indexed as

Signal TransductionADAM ProteinsAnimalsBrain NeoplasmsCell Line, TumorFeedback, PhysiologicalFemaleFibroblast Growth Factor 2GlioblastomaHumansMicroRNAsNeoplasm TransplantationNeoplastic Stem CellsReceptor, Fibroblast Growth Factor, Type 1Zinc Finger E-box-Binding Homeobox 1ADAM ProteinsdecysinFGFR1 protein, humanFibroblast Growth Factor 2MicroRNAsMIRN203 microRNA, humanReceptor, Fibroblast Growth Factor, Type 1ZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1

Identifiers

PMID31434712
PMCPMC7400732
OpenAlexW2969865093

What OpenQuestion holds

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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.