MELK inhibition targets cancer stem cells through downregulation of SOX2 expression in head and neck cancer cells.
Oncol Rep
; 41(4): 2540-2548, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30720113
ABSTRACT
Maternal embryonic leucine zipper kinase (MELK) has been reported to serve critical roles in the maintenance of stemness of cancer cells, although its mechanism remains unclear. Since SRYbox 2 (SOX2) was demonstrated to be involved in selfrenewal and tumorigenicity of head and neck squamous cell carcinoma (HNSCC) and is aberrantly expressed in HNSCC tumors, the association between MELK and SOX2 was examined. Firstly, MELK inhibition was performed by small interfering RNA or MELK inhibitor OTS167, and it was determined that MELK inhibition by these approaches could decrease the SOX2 expression in HNSCC cells and OTS167 could suppress the SOX2 expression in a dosedependent manner. The present results indicated that MELK inhibition may target cancer stem cells (CSCs) through downregulation of the SOX2 gene. To further confirm the transcriptional regulation of SOX2, the transcription factors (TFs) were screened for SOX2 using a promoterbinding TF assay followed by reverse transcriptionquantitative polymerase chain reaction and a decrease of the majority of the SOX2 TFs following MELK knockdown was observed. The present results provide evidence that MELK serves a key role in CSCs through the regulation of SOX2 and further indicates that MELK inhibition may also be promising for clinical applications in the treatment of HNSCC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Regulação Neoplásica da Expressão Gênica
/
Proteínas Serina-Treonina Quinases
/
Fatores de Transcrição SOXB1
/
Neoplasias de Cabeça e Pescoço
Limite:
Humans
Idioma:
En
Revista:
Oncol Rep
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos