The MAP3K1/c-JUN signaling axis regulates glioblastoma stem cell invasion and tumor progression.
Biochem Biophys Res Commun
; 612: 188-195, 2022 07 05.
Article
in En
| MEDLINE
| ID: mdl-35567901
ABSTRACT
Glioblastoma (GBM) stem cells (GSCs) are responsible for GBM initiation, progression, infiltration, standard therapy resistance, and recurrence. However, the mechanisms underlying GSC invasion remain incompletely understood. Using public single-cell RNA-Seq data, we identified MAP3K1 as a master regulator of infiltrative GSCs through c-JUN signaling regulation. MAP3K1 knockdown significantly decreased GSC invasion capacity, proliferation, and stemness in vitro. Moreover, in an orthotopic xenograft model, knockdown of MAP3K1 prominently suppressed GSC infiltration along the corpus callosum and tumor progression and prolonged mouse survival. Mechanistically, MAP3K1 regulates GSC invasion through phosphorylation of downstream c-JUN at serine 63 and 73, as confirmed using the CPTAC phosphoproteome dataset. Furthermore, the c-JUN inhibitor JNK-IN-8 significantly decreased GSC invasion, proliferation, and stemness. Taken together, our study demonstrates that MAP3K1 regulates GSC invasion and tumor progression via activation of c-JUN signaling and indicates that the MAP3K1/c-JUN signaling axis is a therapeutic target for infiltrative GBM.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Glioblastoma
/
MAP Kinase Kinase Kinase 1
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2022
Document type:
Article
Affiliation country:
China