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ADAMDEC1 Maintains ...
ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells
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- Jimenez-Pascual, Ana (författare)
- Cardiff Univ, European Canc Stem Cell Res Inst, Sch Biosci, Cardiff, S Glam, Wales
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- Hale, James S. (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA; Case Comprehens Canc Ctr, Cleveland, OH USA
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- Kordowski, Anja (författare)
- Cardiff Univ, European Canc Stem Cell Res Inst, Sch Biosci, Cardiff, S Glam, Wales
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- Pugh, Jamie (författare)
- Cardiff Univ, European Canc Stem Cell Res Inst, Sch Biosci, Cardiff, S Glam, Wales
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- Silver, Daniel J. (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA; Case Comprehens Canc Ctr, Cleveland, OH USA
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- Bayik, Defne (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA; Case Comprehens Canc Ctr, Cleveland, OH USA
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- Roversi, Gustavo (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA
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- Alban, Tyler J. (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA; Case Comprehens Canc Ctr, Cleveland, OH USA; Case Western Reserve Univ, Dept Mol Med, Cleveland Clin, Lerner Coll Med, Cleveland, OH USA
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- Rao, Shilpa (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA; Case Comprehens Canc Ctr, Cleveland, OH USA
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- Chen, Rui (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA
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- McIntyre, Thomas M. (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA; Case Comprehens Canc Ctr, Cleveland, OH USA; Case Western Reserve Univ, Dept Mol Med, Cleveland Clin, Lerner Coll Med, Cleveland, OH USA
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- Colombo, Giorgio (författare)
- Univ Pavia, Dept Chem, Milan, Italy; ICRM CNR, Inst Mol Recognit Chem, Milan, Italy
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- Taraboletti, Giulia (författare)
- Ist Ric Farmacol Mario Negri IRCCS, Bergamo, Italy
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- Holmberg, Karl O. (författare)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab,Fredrik Swartling
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- Forsberg Nilsson, Karin, 1963- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Lathia, Justin D. (författare)
- Cleveland Clin, Lerner Res Inst, Dept Cardiovasc & Metab Sci, Cleveland, OH USA; Case Comprehens Canc Ctr, Cleveland, OH USA; Case Western Reserve Univ, Dept Mol Med, Cleveland Clin, Lerner Coll Med, Cleveland, OH USA
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- Siebzehnrubl, Florian A. (författare)
- Cardiff Univ, European Canc Stem Cell Res Inst, Sch Biosci, Cardiff, S Glam, Wales
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(creator_code:org_t)
- 2019
- 2019
- Engelska.
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Ingår i: Cancer Discovery. - 2159-8274 .- 2159-8290. ; 9:11, s. 1574-1589
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Jimenez-Pascual, ...
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Hale, James S.
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Kordowski, Anja
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Pugh, Jamie
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Silver, Daniel J ...
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Bayik, Defne
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visa fler...
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Roversi, Gustavo
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Alban, Tyler J.
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Rao, Shilpa
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Chen, Rui
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McIntyre, Thomas ...
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Colombo, Giorgio
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Taraboletti, Giu ...
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Holmberg, Karl O ...
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Forsberg Nilsson ...
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Lathia, Justin D ...
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Siebzehnrubl, Fl ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Cancer Discovery
- Av lärosätet
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Uppsala universitet