Kinome-wide shRNA screen identifies the receptor tyrosine kinase AXL as a key regulator for mesenchymal glioblastoma stem-like cells.
Stem Cell Reports
; 4(5): 899-913, 2015 May 12.
Article
em En
| MEDLINE
| ID: mdl-25921812
ABSTRACT
Glioblastoma is a highly lethal cancer for which novel therapeutics are urgently needed. Two distinct subtypes of glioblastoma stem-like cells (GSCs) were recently identified mesenchymal (MES) and proneural (PN). To identify mechanisms to target the more aggressive MES GSCs, we combined transcriptomic expression analysis and kinome-wide short hairpin RNA screening of MES and PN GSCs. In comparison to PN GSCs, we found significant upregulation and phosphorylation of the receptor tyrosine kinase AXL in MES GSCs. Knockdown of AXL significantly decreased MES GSC self-renewal capacity in vitro and inhibited the growth of glioblastoma patient-derived xenografts. Moreover, inhibition of AXL with shRNA or pharmacologic inhibitors also increased cell death significantly more in MES GSCs. Clinically, AXL expression was elevated in the MES GBM subtype and significantly correlated with poor prognosis in multiple cancers. In conclusion, we identified AXL as a potential molecular target for novel approaches to treat glioblastoma and other solid cancers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Proteínas Proto-Oncogênicas
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Receptores Proteína Tirosina Quinases
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RNA Interferente Pequeno
Limite:
Animals
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Humans
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China