Transcriptional control of brain tumor stem cells by a carbohydrate binding protein.
Cell Rep
; 36(9): 109647, 2021 08 31.
Article
em En
| MEDLINE
| ID: mdl-34469737
ABSTRACT
Brain tumor stem cells (BTSCs) and intratumoral heterogeneity represent major challenges in glioblastoma therapy. Here, we report that the LGALS1 gene, encoding the carbohydrate binding protein, galectin1, is a key regulator of BTSCs and glioblastoma resistance to therapy. Genetic deletion of LGALS1 alters BTSC gene expression profiles and results in downregulation of gene sets associated with the mesenchymal subtype of glioblastoma. Using a combination of pharmacological and genetic approaches, we establish that inhibition of LGALS1 signaling in BTSCs impairs self-renewal, suppresses tumorigenesis, prolongs lifespan, and improves glioblastoma response to ionizing radiation in preclinical animal models. Mechanistically, we show that LGALS1 is a direct transcriptional target of STAT3 with its expression robustly regulated by the ligand OSM. Importantly, we establish that galectin1 forms a complex with the transcription factor HOXA5 to reprogram the BTSC transcriptional landscape. Our data unravel an oncogenic signaling pathway by which the galectin1/HOXA5 complex maintains BTSCs and promotes glioblastoma.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Células-Tronco Neoplásicas
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Neoplasias Encefálicas
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Glioblastoma
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Galectina 1
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá