SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7.
Cell Death Dis
; 13(2): 174, 2022 02 23.
Article
em En
| MEDLINE
| ID: mdl-35197448
ABSTRACT
Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Fator de Transcrição E2F7
/
Neuroblastoma
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article