S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma.
Cancer Res
; 77(19): 5360-5373, 2017 10 01.
Article
en En
| MEDLINE
| ID: mdl-28807938
ABSTRACT
Glioma stem cells (GSC) and epithelial-mesenchymal transition (EMT) are strongly associated with therapy resistance and tumor recurrence, but the underlying mechanisms are incompletely understood. Here, we show that S100A4 is a novel biomarker of GSCs. S100A4+ cells in gliomas are enriched with cancer cells that have tumor-initiating and sphere-forming abilities, with the majority located in perivascular niches where GSCs are found. Selective ablation of S100A4-expressing cells was sufficient to block tumor growth in vitro and in vivo We also identified S100A4 as a critical regulator of GSC self-renewal in mouse and patient-derived glioma tumorspheres. In contrast with previous reports of S100A4 as a reporter of EMT, we discovered that S100A4 is an upstream regulator of the master EMT regulators SNAIL2 and ZEB along with other mesenchymal transition regulators in glioblastoma. Overall, our results establish S100A4 as a central node in a molecular network that controls stemness and EMT in glioblastoma, suggesting S100A4 as a candidate therapeutic target. Cancer Res; 77(19); 5360-73. ©2017 AACR.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
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Neoplasias Encefálicas
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Biomarcadores
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Glioblastoma
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Transición Epitelial-Mesenquimal
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Proteína de Unión al Calcio S100A4
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Res
Año:
2017
Tipo del documento:
Article